Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research.

Animals protect themselves against pathogens or abiotic factors by innate or adaptive mechanisms. Long-chain polyunsaturated fatty acids (ω3) of microalgae modify both human and mice' immune systems resulting in a beneficial balance between pro-inflammatory and anti-inflammatory pathways. However, scarce information exists on their impact on lactating animals' immunity. The objective of this study was to investigate the impact of dietary inclusion of Schizochytrium sp. (rich in docosapentaenoic and docosahexaenoic acid), on the expression of several genes involved in the innate immunity of goats. Twenty-four dairy goats were divided into four homogeneous sub-groups (n = 6). All goats were fed individually with alfalfa hay and concentrate. The concentrate of the control group (CON) had no microalgae while those of the treated groups were supplemented daily with 20 (ALG20), 40 (ALG40), and 60 (ALG60) g Schizochytrium sp. Monocytes and neutrophils were isolated from goats' blood in the 20th, 40th^, and 60th days from the beginning of the experimental period. The relative transcript levels of TLR4, MYD88, MAPK, IRF3, IFNG, and pro-inflammatory cytokines (IL1B, IL2, IL8, TNF), and chemokines (CCL5 and CXCL16) were decreased in monocytes of microalgae treated goats compared to the CON. In contrast, MAPK and IL1B relative transcript levels were increased in neutrophils of ALG40 and ALG60 groups. In conclusion, the supplementation of goats' diet with 20 g Schizochytrium sp. resulted in a downregulation of the pro-inflammatory transcriptions, and following further research could be considered as a sustainable alternative strategy to improve immune function.

Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials.gov Identifier: NCT00396643). In a longitudinal design we measured plasma levels of the pro-inflammatory interleukin 6 (IL-6), the soluble alpha (Tac) subunit of the interleukin 2 receptor (sIL-2r), and the circulating soluble form of the intercellular adhesion molecule one (sICAM-1), in 79 help-seeking UHR individuals (13-25years of age). Using linear mixed model (LMM) analysis, we investigated the effects of 12weeks supplementation of either 1.2g/d PUFA (n=38) or Placebo (n=41). At baseline, inflammatory markers were not altered in patients who later suffered transition to psychosis within one year (n=12; 11 PUFA-group, 1 PL-group). IL-6 was weakly inverse associated with omega-6 PUFA, and highly increased in nicotine users. In univariate tests of the LMM omega-3 PUFA caused a significant increase of sICAM-1 (p=0.022). PUFA did not significantly influence IL-6 or sIL-2r. The enhancement of sICAM-1 in the PUFA condition is suggestive for supportive effects on vascular immune response and immediate Th1 helper cell mediated immune answer, which was found disturbed in manifest schizophrenia, e.g. by facilitating the leukocyte adhesion and migration across the endothelium.

The incorporation of lipid emulsions in parenteral diets is a requirement for energy and essential fatty acid supply to critically ill patients. In this study, the toxicity of a lipid emulsion rich (60%) in triacylglycerol of omega-6 polyunsaturated fatty acids on leukocytes from healthy volunteers was investigated.

Eleven volunteers were recruited, and blood samples were collected before infusion of a soybean oil emulsion, immediately afterwards, and 18 hours later. The cells were studied immediately after isolation and again after 24 hours or 48 hours in culture. The following determinations were made: composition and concentration of fatty acids in plasma, lymphocytes and neutrophils, lymphocyte proliferation, levels of cell viability, DNA fragmentation, phosphatidylserine externalization, mitochondrial depolarization, reactive oxygen species production, and neutral lipid accumulation.

Soybean oil emulsion decreased lymphocyte proliferation and provoked neutrophil and lymphocyte apoptosis and necrosis. Evidence is presented herein that soybean oil emulsion is less toxic to neutrophils than to lymphocytes. The mechanism of cell death induced by this oil emulsion was characterized by mitochondrial membrane depolarization and neutral lipid accumulation but did not alter reactive oxygen species production.

Soybean oil emulsion given as a single dose of 500 mL promotes lymphocyte and neutrophil death that may enhance the susceptibility of the patients to infections.

Rodent and clinical studies have documented that myeloid cell infiltration of tumors is associated with neutrophilia, lymphocytopenia and poor patient outcomes. This contrasts with lymphocyte infiltration of tumors, which is associated with improved outcomes. Lifestyle parameters such as high fat diet s and omega (ω)-6 polyunsaturated fatty acids (PUFA) intake may influence these inflammatory parameters including extramedullary myelopoiesis that can contribute to a metastatic "niche". While, tumor secretion of growth factors (GFs) and chemokines regulate tumor-immune-cell crosstalk, in this chapter, we also emphasize how lifestyle choices, including, obesity, high-fat and high ω-6 PUFA dietary content, contribute to inflammation and myeloid cell infiltration of tumors. A relationship between obesity and high-fat diets (notably the saturated fats in Western diets) and tumor incidence, metastasis, and poor outcomes is generally accepted. However, the mechanisms of dietary promotion of inflammatory microenvironments and targeted drugs to inhibit the clinical sequel remain an unmet challenge. One approach, modification of dietary intake may have a preventative or therapeutic approach to regulate tumor-associated inflammation and remains an attractive, but little studied intervention.

To systematically review the effects of omega-3 poly unsaturated fatty acids (FA) enriched nutrition support on the mortality of critically illness patients.

Databases of Medline, ISI, Cochrane Library, and Chinese Biomedicine Database were searched and randomized controlled trials (RCTs) were identified. We enrolled RCTs that compared fish oil enriched nutrition support and standard nutrition support. Major outcome is mortality. Methodological quality assessment was conducted based on Modified Jadad's score scale. For control heterogeneity, we developed a method that integrated I2 test, nutritional support route subgroup analysis and clinical condition of severity. RevMan 5.0 software (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for meta-analysis.

Twelve trials involving 1208 patients that met all the inclusion criteria. Heterogeneity existed between the trials. A random model was used, there was no significant effect on mortality RR, 0.82, 95% confidence interval (CI) (0.62, 1.09), p = 0.18. Knowing that the route of fish oil administration may affect heterogeneity, we categorized the trials into two sub-groups: parenteral administration (PN) of omega-3 and enteral administration (EN) of omega-3. Six trials administered omega-3 FA through PN. Pooled results indicated that omega-3 FA had no significant effect on mortality, RR 0.76, 95% CI (0.52, 1.10), p = 0.15. Six trials used omega-3 fatty acids enriched EN. After excluded one trial that was identified as source of heterogeneity, pooled data indicated omega-3 FA enriched EN significant reduce mortality, RR=0.69, 95% CI [0.53, 0.91] (p = 0.007).

Omega-3 FA enriched nutrition support is safe. Due to the limited sample size of the included trials, further large-scale RCTs are needed.

The term "enhanced recovery programme (ERP)" means applying defined protocols to augment the recovery of patients following surgery. Inflammation is body's response to insults such as infection, injury and surgical procedures. Inflammatory mediators whose function is initially protective may cause undesirable consequences, if the response is unnecessarily prolonged. The principle effects of ERP result from the reduction of the profound stress which results following major surgical procedures.

A Pubmed literature search was undertaken using the keywords enhanced recovery, surgery and omega-3. The primary endpoint was whether the addition of omega-3 to ERP improved morbidity and mortality.

Nine randomised trials examining the effect of omega-3 enriched diets following surgery were analysed. Inclusion of omega-3 helps in maintaining a positive nitrogen balance, overcome immune dysfunction, lower the incidence of post-operative infections with the consequence of reduced morbidity and mortality.

The provision of early or continuous nutrition is one of the cornerstones of an ERP. A theoretically ideal regimen would provide an energy substrate and protein and contain a component which would limit inappropriate inflammation. The beneficial role of omega-3 results from a number of effects which limit the inflammatory response, principally by influencing the production of eicosanoids and modulating cytokines. They also enhance cell-mediated immunity and preserve immune function better than standard dietary formulations. Although ERPs have already produced significant progress, there is sufficient evidence to suggest that the provision of omega-3 fatty acids may result in further improvements.

No consensus has been reached concerning the effects of preoperative immunonutrition in patients undergoing hepatectomy. We evaluated the effects of immunonutrition before hepatectomy on perioperative management. This study was performed as a randomized controlled trial. Patients expected to undergo segmentectomy or more extensive hepatectomy for liver tumors were randomized to immunonutrition (IM) and control (C) groups each consisting of 13 patients. The IM group was given 750 ml of IMPACT in addition to half-size hospital meals orally from 5 days before to the day before surgery, and the C group was given conventional hospital meals. The blood level of eicosapentaenoic acid was elevated preoperatively in all patients of the IM group. The white blood cell count and interleukin 6 levels, which are indices of postoperative inflammation, were significantly lower in the IM group. As regards liver function, postoperative increases in the aspartate aminotransferase and alanine aminotransaminase levels were slightly suppressed in the IM group. No significant difference was noted in postoperative complications or duration of postoperative hospital stay. In patients undergoing hepatectomy, preoperative immunonutrition reduced inflammation and protected against liver dysfunction.

Schizophrenia (SZ) is a brain disorder that has been intensively studied for over a century; yet, its etiology and multifactorial pathophysiology remain a puzzle. However, significant advances have been made in identifying numerous abnormalities in key biochemical systems. One among these is the antioxidant defense system (AODS) and redox signaling. This review summarizes the findings to date in human studies. The evidence can be broadly clustered into three major themes: perturbations in AODS, relationships between AODS alterations and other systems (i.e., membrane structure, immune function, and neurotransmission), and clinical implications. These domains of AODS have been examined in samples from both the central nervous system and peripheral tissues. Findings in patients with SZ include decreased nonenzymatic antioxidants, increased lipid peroxides and nitric oxides, and homeostatic imbalance of purine catabolism. Reductions of plasma antioxidant capacity are seen in patients with chronic illness as well as early in the course of SZ. Notably, these data indicate that many AODS alterations are independent of treatment effects. Moreover, there is burgeoning evidence indicating a link among oxidative stress, membrane defects, immune dysfunction, and multineurotransmitter pathologies in SZ. Finally, the body of evidence reviewed herein provides a theoretical rationale for the development of novel treatment approaches.

The purpose of this paper is to investigate the possible role of immunonutrition in head and neck cancer patients. Malnutrition frequently occurs in head and neck oncological patients, due to mechanical obstruction, such as tumour induced cachexia, poor dietary habits, as well as excessive alcohol consumption. These defects combined with the immune suppressive effects of surgery have been claimed to contribute in increasing the postoperative complications rate, such as poor wound healing and higher incidence of infections. Immunonutrition has been proposed to provide specific benefits to the immune system; several clinical trials, also in head and neck cancer patients, are already present in the literature, even if methodological differences impede comparisons and firm conclusions so far. Nutritional oncology is a new and interesting field and requires the use of standardised intervention protocols in order to evaluate its clinical efficacy.

Many macrophage functions are modulated by fatty acids (FAs), including cytokine release, such as tumor necrosis factor-α (TNF-α). TNF-α is of great interest due to its role in the inflammation process observed in several diseases such as rheumatoid arthritis, atherosclerosis, and obesity. However, the mechanisms by which FA effects occur have not been completely elucidated yet. In this study, we used a mouse monocyte lineage (J774 cells) to evaluate the effect of 50 and 100 μM of saturated (palmitic and stearic acids), monounsaturated (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-α production. Alterations in gene expression, poly(A) tail length and activation of transcription factors were evaluated. Oleic and linoleic acids, usually known as neutral or pro-inflammatory FA, inhibited LPS-induced TNF-α secretion by the cells. Saturated FAs were potent inducers of TNF-α expression and secretion under basal and inflammatory conditions (in the presence of LPS). Although the effect of the saturated FA was similar, the mechanism involved in each case seem to be distinct, as palmitic acid increased EGR-1 and CREB binding activity and stearic acid increased mRNA poly(A) tail. These results may contribute to the understanding of the molecular mechanisms by which saturated FAs modulate the inflammatory response and may lead to design of associations of dietary and pharmacological strategies to counteract the pathological effects of TNF-α.

This study aimed to systematically review the clinical efficacy of lipid emulsion containing fish oil in surgical patients.

Medline, SCI, Embase, Cochrane Library, and Chinese Biomedicine Database were searched for studies published before January 1, 2009 that were randomized controlled trials for postoperative patients. Parenteral nutrition with or without fish oil emulsion was the only difference between the intervention and control groups. Methodologic quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 and Jadad's score scale. RevMan 5.0 statistical software was used for meta-analysis.

Six trials met all inclusion criteria and were enrolled for final meta-analysis. The aggregated results of the trails showed that fish oil was associated with no mortality advantage. There was a significant reduction in infectious complications in patients receiving fish oil (relative risk 0.49, 95% confidence interval 0.26-0.93, P=0.03). The result on length of hospital stay showed a trend of shortening by 3.06 d associated with receiving fish oil. However, the difference was not significant. When excluding one obviously heterogeneous study and aggregating the other three remaining studies, results showed significantly shortening of length of hospital stay associated with receiving fish oil. Fish oil also significantly shortened length of stay in the intensive care unit by 2.07 d.

The administration of lipid emulsion containing fish oil to patients undergoing elective major operations improves outcomes. The infectious complications are significantly fewer and length of hospitalization significantly shortened for patients treated with lipid emulsion containing fish oil. Further well-designed randomized controlled trials are needed to demonstrate the cost effectiveness of lipid emulsion containing fish oil to postoperative patients.

The mechanisms of immunonutrition on reducing infectious complications are still poorly understood. This prospective randomized study was designed to determine whether immunonutrition influences the following factors: cell-mediated immunity, differentiation of T helper type 1 (Th1) and Th2 cells, interleukin (IL)-17-producing CD4(+) helper T (Th17) cell response, and infectious complication rate after pancreaticoduodenectomy.

Thirty patients who underwent pancreaticoduodenectomy were divided into 3 groups. Ten patients in the perioperative group received immune-enhancing diets enriched with arginine, omega-3 fatty acids, and RNA for 5 days before operative resection, which was prolonged after operative resection by enteral infusion. Ten patients in the postoperative group received early postoperative enteral infusion of the same enriched formula with no artificial nutrition before operative resection. Ten patients in the control group received total parenteral nutrition postoperatively. The primary endpoint was immune responses; the secondary endpoint was the rate of infectious complications.

Concanavalin A (Con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation and natural killer cell activity were significantly higher in the perioperative group than in the other groups. Messenger RNA (mRNA) expression levels of T-bet, interferon-gamma (IFN-gamma), related orphan receptor gammat (RORgammat), and interleukin-17F (IL-17F) were significantly higher in the perioperative group than in the other groups. In the perioperative group, the rate of infectious complications was significantly reduced compared with that in the other groups.

Perioperative immunonutrition reduced stress-induced immunosuppression after a major stressful operative resection. The modulation of Th1/Th2 differentiation and Th17 response may play important roles in this immunologic effect.

Despite the lack of robust evidence, there has been a steady increase in the use of dietary supplements, including Omega 3 fatty acids and antioxidants, in the management of musculoskeletal conditions. One reason for this is that unsatisfactory outcomes with conventional treatments have lead sufferers to seek alternative solutions including the use of nutritional supplements. In the United Kingdom alone, the current supplement market is estimated to be over 300 pounds million per annum. One target market for nutritional supplements is tendinopathies including conditions involving the rotator cuff. This condition is debilitating and associated with considerable morbidity. Incidence increases with advancing age. High levels of cytokines, such as the pro-inflammatory interleukin 1 beta and vascular endothelial growth factor, have been reported within the bursa of patients with rotator cuff disease. There is also evidence that high concentrations of free-radical oxidants may also be involved in tendon pathology. Therefore, the possibility exists that dietary supplements may have a beneficial effect on tendon pathology, including that of the rotator cuff. A review was conducted to synthesize the available research literature on the histopathology of rotator cuff disease and the effectiveness of polyunsaturated fatty acids (PUFAs) and antioxidants on tendinopathies. A search was conducted using the MEDLINE, CINAHL, AMED, EMBASE, Cochrane, and PEDro databases using the terms "rotator cuff" and "tear/s" and "subacromial impingement syndrome," "burase," "bursitis," "tendinopathy," "tendinitis," "tendinosis," "polyunsaturated fatty acids," "PUFA," "Omega 3," "histopathology," "etiology," and "antioxidants." English language was an inclusion criterion. There were no randomized clinical trials found relating specifically to the rotator cuff. Only one trial was found that investigated the efficacy of PUFAs and antioxidants on tendinopathies. The findings suggest that some (low level) evidence exists to support the supplementation in the management of tendinopathies. Any conclusions based on this one article should be reached with caution. Subsequently, there is a distinct and clear need for well-planned randomized controlled trials that aim to investigate the efficacy of supplements in the management of tendinopathies including those of the rotator cuff.

The higher incidence of inflammatory diseases in Western countries might be related, in part, to a high consumption of saturated fatty acids and n-6 polyunsaturated fatty acids (PUFA) and an insufficient intake of n-3 fatty acids. The purpose of this study was to examine the effects of dietary n-3 fatty acids on innate and specific immune response and their anti-inflammatory action in models of contact and atopic dermatitis. Balb/C mice were fed for 3 wk either n-6 or n-3 PUFA-fortified diets. After inducing a contact or an atopic dermatitis, immunological parameters were analyzed to evaluate the anti-inflammatory potential of these n-3 PUFA. n-3 PUFA reduced innate and specific immune responses through inhibition of TH1 and TH2 responses, increase of immunomodulatory cytokines such as IL-10, and regulation of gene expression. The inhibition of both kinds of responses was confirmed by the anti-inflammatory effect observed in contact and atopic dermatitis. Reduction in weight, edema, thickness, leukocyte infiltration, and enhancement of antioxidant defenses in the inflamed ears of mice from both models along with the prevention of delayed-type hypersensitivity induced in atopic dermatitis proved n-3 PUFA efficacy. Our data suggest that dietary fish oil-derived n-3 fatty acids have immunomodulatory effects and could be useful in inflammatory disorders.

In the present study, the cytotoxicity of palmitic, stearic, oleic, linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids on a macrophage cell line (J774) was investigated. The induction of toxicity was investigated by changes in cell size, granularity, membrane integrity, DNA fragmentation and phosphatidylserine externalization by using flow cytometry. Fluorescence microscopy was used to determine the type of cell death (Acridine Orange/ethidium bromide assay). The possible mechanisms involved were examined by measuring mitochondrial depolarization, lipid accumulation and PPARgamma (peroxisome-proliferator-activated receptor gamma) activation. The results demonstrate that fatty acids induce apoptosis and necrosis of J774 cells. At high concentrations, fatty acids cause macrophage death mainly by necrosis. The cytotoxicity of the fatty acids was not strictly related to the number of double bonds in the molecules: palmitic acid>docosahexaenoic acid>stearic acid=eicosapentaenoic acid=arachidonic acid>oleic acid>linoleic acid. The induction of cell death did not involve PPARgamma activation. The mechanisms of fatty acids to induce cell death involved changes in mitochondrial transmembrane potential and intracellular neutral lipid accumulation. Fatty acids poorly incorporated into triacylglycerol had the highest toxicity.

Fish oil (FO) has been shown to modulate the acute and chronic inflammatory responses. Endotoxin (LPS) has been shown to mimic several aspects of sepsis. The study aimed at testing the effects of oral FO supplements in healthy subjects submitted to intravenous LPS on systemic and endocrine response.

Fifteen healthy men (aged 26.0+/-3.1 years, BMI 23.8+/-1.9 kg/m2), were enrolled. Subjects were randomised to 3-4 weeks of oral FO supplementation (7.2 g/day, providing 1.1 g/day of 20:5 (n-3) and 0.7 g/day of 22:6 (n-3) fatty acids) or no supplementation and then submitted to endotoxin challenge: 2 ng/kg of LPS. All subjects were studied twice (placebo and LPS).

vital signs, energy expenditure (EE), glucose and lipid metabolism ((2)H2-glucose), plasma cytokines and stress hormones for 6 h after LPS or placebo.

LPS caused cytokine release, fever, increases in heart rate, resting EE and substrate oxidation, plasma glucagon and glucose concentrations; the neuro-endocrine response was characterised by increased plasma stress hormones. FO significantly blunted fever, ACTH and cortisol plasma levels (no effect on cytokine release). FO blunted the peak norepinephrine after LPS.

FO supplements blunted the endocrine stress response and the increase in body temperature, but had no impact on cytokine production after LPS. These findings conflict with the postulated anti-inflammatory effects of FO on arachidonic acid metabolism and cytokine release. These results suggest that FO may exert beneficial effects in sepsis though non-inflammatory which require further investigations.

Modulation of macrophage functions by fatty acids (FA) has been studied by several groups, but the effect of FA on nitric oxide production by macrophages has been poorly examined. In the present study the effect of palmitic, stearic, oleic, linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids on NF-kappaB activity and NO production in J774 cells (a murine macrophage cell line) was investigated. All FA tested stimulated NO production at low doses (1-10 microM) and inhibited it at high doses (50-200 microM). An increase of iNOS expression and activity in J774 cells treated with a low concentration of FA (5 microM) was observed. The activity of NF-kappaB was time-dependently enhanced by the FA treatment. The inhibitory effect of FA on NO production may be due to their cytotoxicity, as observed by loss of membrane integrity and/or increase of DNA fragmentation in cells treated for 48 h with high concentrations. The results indicate that, at low concentrations FA increase NO production by J774 cells, whereas at high concentrations they cause cell death.

Acute tubular necrosis (ATN) is a form of acute renal failure (ARF) that is common in hospitalized patients. In critical care units, it accounts for about 76% of cases of ARF. Despite the introduction of hemodialysis > 30 years ago, the mortality rates from ATN in hospitalized and ICU patients are about 37.1% and 78.6%, respectively. The purpose of this review is to discuss briefly the cause, diagnosis, and epidemiology of ARF, and to review in depth the clinical trials performed to date that have examined the influence of growth factors, hormones, antioxidants, diuretics, and dialysis. In particular, the role of the dialysis modality, dialyzer characteristics, and dosing strategies are discussed.

Propofol (2,6-diisopropylphenol) is a potent intravenous hypnotic agent widely administered for induction and maintenance of anesthesia and for sedation in the intensive care unit. Propofol is insoluble in water and therefore is formulated in a lipid emulsion. In addition, a preservative (ethylenediaminetetraacetic acid [EDTA] or sodium metabisulfite) is added to retard bacterial growth. Propofol has antiinflammatory properties, decreasing production of proinflammatory cytokines, altering expression of nitric oxide, and inhibiting neutrophil function. Propofol also is a potent antioxidant. The added preservatives have biologic activity; EDTA has antiinflammatory properties, whereas metabisulfite may cause lipid peroxidation. The antiinflammatory and antioxidant properties of propofol may have beneficial effects in patients with sepsis and systemic inflammatory response syndrome.

Alpha-linolenic acid (18:3omega3) has many important physiological functions including being beta-oxidized, serving a precursor to the synthesis of other lipids and it has immunomodulation properties. The objective of the present study was to test the effects of immunization and dietary 18:3omega3 on immune function and the fatty acid profile of immunized pig tissues. Piglets suckled from sows consuming either a control or high 18:3omega3 diet until 14 days old when they were weaned onto a similar diet as the sow and were moved to a segregated nursery for the remainder of the study. At 35 days of age, pigs on both diets (2 x 2 factorial design) received either an injection containing hen eggwhite lysozyme (HEWL), killed Mycobacterium tuberculosis and Freund's complete adjuvant (immunized) or phosphate buffered saline (PBS) (non-immunized) into the neck followed by a booster injection 2 weeks later and induction of delayed-type hypersensitivity (DTH) one week later. Immunization increased (compared to non-immunized) while the high 18:3omega3 diet decreased haptoglobin by 30% compared to pigs consuming the control diet. Immunized pigs had a seven-fold increase in antibodies to HEWL and pigs consuming the high 18:3omega3 diet also had transiently higher levels of serum antibodies. There was a diet by immunization interaction on the DTH reaction such that immunized pigs consuming the high 18:3omega3 had the largest DTH reaction. The neck muscle proximal to the site of injection of immunized pigs had 10-30% lower levels of triglyceride and phospholipid linoleic (18:2omega6) and 18:3omega3 compared to non-immunized pigs. Thus, a high 18:3omega3 intake in pigs modulates immune function and tissue fatty acids in response to immunization.

Over the last 25 years, the effects of fatty acids on the immune system have been characterized using in vitro, animal and human studies. Advances in fatty acid biochemistry and molecular techniques have recently suggested new mechanisms by which fatty acids could potentially modify immune responses, including modification of the organization of cellular lipids and interaction with nuclear receptors. Possibilities for the clinical applications of n-3 PUFA are now developing. The present review focuses on the hypothesis that the anti-inflammatory properties of n-3 PUFA in the arterial wall may contribute to the protective effects of n-3 PUFA in CVD, as suggested by epidemiological and secondary prevention studies. Studies are just beginning to show that dietary n-3 PUFA can be incorporated into plaque lipid in human subjects, where they may influence the morphology and stability of the atherosclerotic lesion.

Findings to date provide evidence that altered membrane structure and function are present in patients with either first-episode or chronic schizophrenia, suggesting defects in phospholipid metabolism and cell signaling in schizophrenia. The purpose of this investigation is to test whether decreased membrane polyunsaturated fatty acids (PUFAs) were associated with an increased secretion of proinflammatory cytokines. Thus, we measured interleukin 6 (IL-6) and interleukin 10 (IL-10) in cerebrospinal fluid (CSF) of patients with chronic schizophrenia as well as PUFAs of red blood cell (RBC) membranes from the same individuals. A significant and inverse correlation was found between CSF IL-6 (not IL-10) and RBC membrane PUFAs levels in both haloperidol-treated and medication-free patients with schizophrenia. Specifically, such an association was found in the n-6 (18:2, 20:4, and 22:4) and, to a lesser extent, the n-3 fatty acids. Taken together, the present findings suggest that decreased membrane PUFAs may be related to an immune disturbance in schizophrenia, possibly resulting from an increased phospholipase A2 activity mediated through the proinflammatory cytokines.

Lipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6). Linoleic acid is the precursor of arachidonic acid (20:4n-6). In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach.

Inflammatory Bowel Diseases - ulcerative colitis and Crohn's disease- are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Total parenteral nutrition has been used to correct and to prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission in adults and promoting growth in children. Due to its low complication rate and lower costs, enteral nutrition should be preferred over total parenteral nutrition whenever possible. Both present equal effectiveness in primary therapy for remission of active Crohn's disease. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need total parenteral nutrition. Recent research has focused on the use of nutrients as primary treatment agents. Immunonutrition is an important therapeutic alternative in the management of inflammatory bowel diseases, modulating the inflammation and changing the eicosanoid synthesis profile. However, beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these and other nutrients (glutamine, short-chain fatty acids, antioxidants) still need further evaluation through prospective and randomized trials.

The immune system is involved in host defense against infectious agents, tumor cells, and environmental insults. Inflammation is an important component of the early immunologic response. Inappropriate or dysfunctional immune responses underlie acute and chronic inflammatory diseases. The n-6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds that have important roles in inflammation and in the regulation of immunity. Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators, through several mechanisms, including decreased availability of AA, competition for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, and decreased expression of COX-2 and 5-LOX. This alone is a potentially beneficial anti-inflammatory effect of n-3 FA. However, n-3 FA have a number of other effects that might occur downstream of altered eicosanoid production or might be independent of this effect. For example, dietary fish oil results in suppressed production of proinflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease and to protect against the effects of endotoxin. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some asthmatics, supporting the idea that the n-3 FA in fish oil are anti-inflammatory. There are indications that the inclusion of fish oil in enteral and parenteral formulae is beneficial to patients.

The n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in high proportions in oily fish and fish oils. The n-3 PUFA are structurally and functionally distinct from the n-6 PUFA. Typically, human inflammatory cells contain high proportions of the n-6 PUFA arachidonic acid and low proportions of n-3 PUFA. The significance of this difference is that arachidonic acid is the precursor of 2-series prostaglandins and 4-series leukotrienes, which are highly-active mediators of inflammation. Feeding fish oil results in partial replacement of arachidonic acid in inflammatory cell membranes by EPA. This change leads to decreased production of arachidonic acid-derived mediators. This response alone is a potentially beneficial anti-inflammatory effect of n-3 PUFA. However, n-3 PUFA have a number of other effects which might occur downstream of altered eicosanoid production or might be independent of this activity. For example, animal and human studies have shown that dietary fish oil results in suppressed production of pro-inflammatory cytokines and can decrease adhesion molecule expression. These effects occur at the level of altered gene expression. This action might come about through antagonism of the effects of arachidonic acid-derived mediators or through more direct actions on the intracellular signalling pathways which lead to activation of transcription factors such as nuclear factor kappa B (NFB). Recent studies have shown that n-3 PUFA can down regulate the activity of the nuclear transcription factor NFB. Fish oil feeding has been shown to ameliorate the symptoms in some animal models of chronic inflammatory disease and to protect against the effects of endotoxin and similar inflammatory challenges. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory. There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.

We previously reported that omega-6 fat emulsion increases cytokine production in burned rats. Effects of soybean oil emulsion on surgical stress responses and lymphocyte function according to the surgical severity have not been studied in detail. We investigated the effects of soybean oil emulsion, which contains 50% omega-6 fatty acid, on postoperative stress responses and cell-mediated immune function according to the severity of surgical stress.

Eight patients who underwent gastric or colorectal surgery and nine who underwent esophagectomy were fed fat-free total parenteral nutrition. Ten patients who underwent gastric or colorectal surgery and seven who underwent esophagectomy were fed total parenteral nutrition with soybean oil emulsion. Total parenteral nutrition provided 1.5 g of protein and 40 kcal per kilogram every day from 7 d before surgery to postoperative day 14. Soybean oil emulsion (Intralipid) accounted for 20% of the total calories. Serum interleukin-6, C-reactive protein, glucagon, and concanavalin A- or phytohemagglutinin-stimulated lymphocyte proliferation were determined.

In the group of moderately stressed patients, soybean oil emulsion did not amplify the measured levels. In the group of severely stressed patients, soybean oil emulsion amplified the level of serum interleukin-6 and decreased concanavalin A- or phytohemagglutinin-stimulated lymphocyte proliferation.

Soybean oil emulsion amplifies the stress responses and possibly suppresses cell-mediated immune function induced by surgical stress in severely stressed patients, but not in moderately stressed patients.

Metabolic changes with burns patients are enormous. The loss of skin substance and the necessity of its reconstruction are at the origin of this exceptional situation. In this context of major aggression with important metabolic alteration the nutritional needs are considerable. To assure a tissue reconstruction, nutrition is as important as the fight against infection. The authors make the point on the quantity needs and the quality needs. They raise up the perspectives concerning immunonutriments and note the importance of enteral administration. As a conclusion, they insist on the fundamental role of the clinical aspect, in the survey of nutritional state.

It has been increasingly reported that administration of n-3 fatty acids is beneficial in patients with inflammatory processes. This effect is most likely caused by different biological characteristics, including an immunomodulating effect of the products derived from n-3 fatty acids through eicosanoid metabolism. The aim of this study was to investigate the effect of perioperative administration of n-3 fatty acids on inflammatory and immune responses as well as on the postoperative course of patients with extended surgical interventions of the abdomen. In particular, the effect of n-3 fatty acids on interleukin-6 release and on granulocyte/monocyte function (HLA-DR expression) was studied. There was a downregulation of the inflammatory response, and, simultaneously, a smaller postoperative immune suppression in the n-3 fatty acid group. In addition, we observed shorter postoperative periods in the intensive care unit and on the regular medical wards as well as lower rates of severe infections. The results suggest that perioperative administration of n-3 fatty acids may have a favourable effect on outcome in patients with severe surgical interventions by lowering the magnitude of inflammatory response and by modulating the immune response.

To study the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) on in vitro proliferation of endometrial cells and their production of the cytokine interleukin-8 (IL-8).

In vitro study.

Obstetrics and gynecology department, University of Aberdeen.

Women attending an infertility clinic.

In vitro cell cultures using culture mediums supplemented with normal and high ratios of omega-3 PUFA and omega-6 PUFA.

In vitro survival and production of IL-8 by dispersed endometrial cells.

In vitro survival of endometrial cells from women with and without endometriosis was significantly reduced in the presence of high omega-3:omega-6 PUFA ratios compared with cells incubated in the absence of fatty acids, in balanced omega-3:omega-6 PUFA ratios, and in high omega-6:omega-3 PUFA ratios. Endometrial cells from women with endometriosis secreted higher concentrations of IL-8, especially in the presence of high omega-3:omega-6 PUFA ratios.

omega-3 PUFA may have a suppressive effect on the in vitro survival of endometrial cells and omega-3 PUFA be useful in the management of endometriosis by reducing the inflammatory response and modulating cytokine function.

The fatty acid composition of inflammatory and immune cells is sensitive to change according to the fatty acid composition of the diet. In particular, the proportion of different types of polyunsaturated fatty acids (PUFA) in these cells is readily changed, and this provides a link between dietary PUFA intake, inflammation, and immunity. The n-6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds, which have important roles in inflammation and in the regulation of immunity. Fish oil contains the n-3 PUFA eicosapentaenoic acid (EPA). Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators. In addition, EPA is a substrate for cyclooxygenase and lipoxygenase and gives rise to mediators that often have different biological actions or potencies than those formed from AA. Animal studies have shown that dietary fish oil results in altered lymphocyte function and in suppressed production of proinflammatory cytokines by macrophages. Supplementation of the diet of healthy human volunteers with fish oil-derived n-3 PUFA results in decreased monocyte and neutrophil chemotaxis and decreased production of proinflammatory cytokines. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease. Clinical studies have reported that fish oil supplementation has beneficial effects in rheumatoid arthritis, inflammatory bowel disease, and among some asthmatics, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory and immunomodulatory.

Elderly patients and those with poor ventricular function have increased morbidity and mortality rates when undergoing surgery. We aimed to ascertain whether an oral immune-enhancing nutritional supplement could improve preoperative host defence, and subsequently lower postoperative infections and organ dysfunction in patients undergoing elective cardiac surgery who are at high risk of infection.

In this prospective, randomised, double-blind, placebo-controlled study, we randomly assigned 50 patients who were scheduled to undergo coronary artery bypass to receive either an oral immune-enhancing nutritional supplement containing L-arginine, omega3 polyunsaturated fatty acids, and yeast RNA (n=25), or a control (n=25) for a minimum of 5 days. Patients were included if they were aged 70 years or older, or had an ejection fraction of less than 0.4, or were scheduled to undergo mitral valve replacement. The main outcome was preoperative host defence (delayed-type hypersensitivity response to recall antigens, expression of HLA-DR epitopes on monocytes, and concentration of interleukin 6 in plasma). Analysis was per protocol.

Five patients (two in the treatment group) were excluded because they did not take the minimum dose. Preoperative expression of HLA-DR epitopes on monocytes was significantly higher in patients given the study treatment (109% [95% CI 92-128]) than those given the control (69% [58-82]) compared with baseline (100%) (p=0.02, repeated measures ANOVA). However, concentration of interleukin 6 was significantly lower in the treatment group (0.90 pg/L [0.69-1.18]) than in the control group (1.94 pg/L [1.45-2.59]) (p=0.032, repeated measures ANOVA). Additionally, delayed-type hypersensitivity response to recall antigens improved preoperatively and remained better until hospital discharge.

Intake of an oral immune-enhancing nutritional supplement for a minimum of 5 days before surgery can improve outlook in high-risk patients who are undergoing elective cardiac surgery.

It has been suggested that dietary fat exacerbates intestinal inflammation. We investigated the effect of fatty acids on interleukin (IL)-8 production in a human intestinal epithelial cell line (Caco-2).

The cells were cultured as monolayers on microporous membranes in culture inserts. Oleic acid (OA), capric acid (CA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were applied to the apical compartment of Caco-2 cell monolayers. The concentration of IL-8 in the basolateral medium was measured by using enzyme-linked immunosorbent assay, and the expression of IL-8 mRNA was measured by using competitive reverse transcription--polymerase chain reaction. Protein kinase C inhibitors (GF109203X and calphostin C) and H-7 (a protein kinase inhibitor) were used to study the mechanisms by which IL-8 production is stimulated.

Both OA and CA enhanced IL-8 production (approximately fivefold), whereas DHA and EPA did not. Both OA and CA also enhanced IL-1-induced IL-8 production. The onset of OA-induced IL-8 production was delayed compared with that of CA-induced IL-8 production. Both OA and CA enhanced IL-8 mRNA expression (approximately fivefold) after 6 and 3 h, respectively. The protein kinase inhibitor (H-7) reduced both OA- and CA-induced IL-8 production by 88.0 and 85.9%, respectively. The protein kinase C inhibitors (GF109203X and calphostin C) reduced OA-induced IL-8 production by 29.3 and 54.5%, respectively, but showed no effect on CA-induced IL-8 production.

These findings suggest that not only OA but also CA stimulates IL-8 production in intestinal epithelial cells, and the mechanisms of action differ between OA and CA.

Burns covering more than 10% of the total body surface area (TBSA) are responsible for systemic perturbations which, in very severe cases, can represent a vital risk and, in all cases, affect the wound evolution. Among these general perturbations, fluid volume and electrolyte changes, leading eventually to burn shock, have the most dramatic consequences. Burn shock is, still to day, a vital risk and can also, in case of inadequate early fluid resuscitation, results in secondary morbidity and mortality. Fluid replacement during the very first hours after injury represents certainly a key point of the management of severe burn cases. Estimation of resuscitation fluid needs during this period is frequently underestimated. For adult, we recommend, during the first hour, a minimum of one liter for all severe injuries and two liters if the injury exceeds 50% of TBSA. Pulmonary injuries due to smoke inhalation are frequent, about 25% of patients hospitalized in burn units, and responsible for numerous death at site of house fires. In burn units, about 25% of hospitalized patients have pulmonary injuries in relation with smoke inhalation. This population has a high mortality rate increasing with the area of the skin injury and with age. Patients with inhalation injury need more resuscitation fluids, are subject to pneumonia and necessitate frequently mechanical ventilation. Parameters of the mechanical ventilation have to be choice to avoid barotrauma. Severe burn patients are submitted to a very high metabolic level. This can leads to a deep nutritional deficit responsible for an immunological suppression. It is then of major importance to provide an adequate nutritional support. It is also necessary to fight against the stress and to put the patient in a warm environment. Finally, infection is the most frequent and the most severe complication of burn injuries. Everything have to be done to avoid bacteriological contamination including architecture, equipment's, care procedure, nutritional support, types of wound dressing and most importantly surgery. Surgical procedures have to be done as earliest as possible to excise necrosis and cover the wound.