• COVID-19
• SIL-1R1
• SIL-1R2
• STNFR1
• STNFR2
• Sepsis

• Humans
• COVID-19/blood
• COVID-19/mortality
• Sepsis/blood
• Male
• Female
• Middle Aged
• Aged
• SARS-CoV-2
• Adult
• Receptors, Tumor Necrosis Factor, Type I/blood
• Leukocytes, Mononuclear/metabolism
• Receptors, Tumor Necrosis Factor/blood
• Receptors, Interleukin-1/blood
• Receptors, Interleukin-1 Type II/blood
• Receptors, Tumor Necrosis Factor, Type II/blood

• severe acute pancreatitis
• biomarkers
• immune markers
• innate immune response

• Humans
• Biomarkers/blood
• Pancreatitis/immunology
• Pancreatitis/blood
• Pancreatitis/diagnosis
• Cytokines/blood
• Cytokines/immunology
• Severity of Illness Index
• Acute Disease
• Inflammasomes/immunology

• R01 DK134698 NIDDK NIH HHS
• U01 DK127388 NIDDK NIH HHS
• U01 DK127404 NIDDK NIH HHS

• ADAM17
• TNF-α converting enzyme
• tuberculosis
• tumor necrosis factor
• tumor necrosis factor receptors

• RANTES
• TNFα
• TNFα-soluble receptors
• celocentesis
• embryogenesis
• extraembryonic celomic fluid
• sTNFR1
• sTNFR2
• tumor necrosis factor alpha

• Female
• Pregnancy
• Humans
• Receptors, Tumor Necrosis Factor, Type II
• Tumor Necrosis Factor-alpha
• Chemokine CCL5
• Biological Availability
• Gestational Sac/metabolism
• T-Lymphocytes/metabolism

• AZD4831
• HFpEF
• heart failure
• inflammation
• microvascular dysfunction
• myeloperoxidase

• chronic inflammation
• cytokine
• cytokine status
• intervertebral disc degeneration
• molecular mechanism
• treatment

• cytokines
• organ failure
• severe pancreatitis
• systemic inflammatory response syndrome

• Humans
• Pancreatitis/complications
• Cytokines/metabolism
• Interleukin-6
• Interleukin-8
• Chemokine CCL2
• Resistin
• Hepatocyte Growth Factor/therapeutic use
• Angiopoietin-2/therapeutic use
• Prospective Studies
• Tumor Necrosis Factor-alpha/metabolism
• Acute Disease
• Biomarkers
• Anti-Inflammatory Agents/therapeutic use

• R56 DK061451 NIDDK NIH HHS
• I01 CX000272 CSRD VA
• R01 DK061451 NIDDK NIH HHS
• HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• U.S. Department of Defense (DOD)
• U.S. Department of Veterans Affairs (VA)

• ADAM
• HIV
• IRIS
• TIM-3
• TNF-α

Guillain-Barré Syndrome (GBS) is currently considered the most common global cause of acute flaccid paralysis. Currently, standard therapy for Guillain-Barré Syndrome includes intravenous immunoglobulin or plasma exchange. Despite medical advances regarding these treatments, many treated patients do not reach full recovery. Therefore several biological agents have attracted the attentions from researchers during the last decades, and various studies have investigated their role in Guillain-Barré Syndrome.

The present study aims to address emerging biological approaches to GBS while considering their efficiency and safety in treating the disease.

An extensive electronic literature search was conducted by two researchers from April 2016 to July 2016. Original articles, clinical trials, systematic reviews (with or without meta-analysis) and case reports were selected. Titles and abstracts of papers were screened by reviewers to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved.

Herein authors focused on the literature data concerning emerging biological therapeutic agents, namely anti-C5 monoclonal antibody (Eculizumab), anti-C1q monoclonal antibody, anti-T cell monoclonal antibody, anti-CD2 monoclonal antibody, anti L-selectin monoclonal antibody, anti-CD20 monoclonal antibody (Rituximab), anti-CD52 monoclonal antibody (Alemtuzumab) and cytokine targets. By far, none of these agents have been approved for the treatment of GBS by FDA.

Literature findings represented in current review herald promising results for using these biological targets. Current review represents a summary of what is already in regards and what progress is required to improve the immunotherapeutic approach of treating GBS via future studies.

• Guillain-barré syndrome
• biological
• drug
• immunotherapy
• monoclonal antibody.
• therapy
• treatment

• Crotalus Neutralizing Factor (CNF)
• Inflammatory mediators
• Neutrophils
• PBMCs

• Animals
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Chemotaxis/drug effects
• Crotalus
• Cytokines/metabolism
• Cytosol/enzymology
• Humans
• Interleukin-10/metabolism
• Interleukin-2/metabolism
• Interleukin-8/metabolism
• Leukocytes, Mononuclear/cytology
• Leukocytes, Mononuclear/drug effects
• Leukocytes, Mononuclear/metabolism
• Leukotriene B4/biosynthesis
• Neutrophils/cytology
• Neutrophils/drug effects
• Neutrophils/metabolism
• Peroxidase/metabolism
• Phospholipase A2 Inhibitors/pharmacology
• Superoxides/metabolism
• Tumor Necrosis Factor-alpha/metabolism

To assess inflammatory serum markers including serum proinflammatory cytokines, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) according to the clinical inflammatory activity of patients with hidradenitis suppurativa (HS).

Seventy-four patients with HS were studied based on the Hidradenitis Suppurativa-Physician Global Assessment (HS-PGA) score and Hurley staging system. Proinflammatory cytokines were measured using a multiplex cytokine assay. Twenty-two healthy volunteers were recruited.

Serum interleukin- (IL-) 6, IL-23, soluble tumour necrosis factor alpha (TNF-α) receptor I (sTNF-RI), CRP, and ESR were different in the patients with HS compared with those in the healthy controls (P < 0.05). The levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, sTNF-RII, CRP, and ESR were significantly elevated according to inflammatory activity based on HS-PGA scores (r > 0.25, P < 0.05). The levels of IL-6 (r = 0.53, P < 0.001), CRP (r = 0.54, P < 0.001), and ESR (r = 0.60, P < 0.001) were especially well correlated with clinical inflammatory activity based on HS-PGA scores. The levels of IL-6, IL-8, sTNF-RI, sTNF-RII, CRP, and ESR were significantly elevated according to Hurley staging system.

Serum proinflammatory cytokines, CRP, and ESR are increased in relation to the clinical inflammatory activity of patients with HS compared with healthy controls. Serum IL-6, CRP, and ESR are effective biomarkers for evaluating the severity of HS.

The pleiotropic activities of TNF are mediated by two structurally related but functionally distinct type I transmembrane receptors, p55TNFR and p75TNFR expressed in most cell types, that can be cleaved and act as TNF scavengers. Here, we investigated the effect of persistent p55TNFR cell surface expression during aerosol inhalation challenge with virulent M. tuberculosis H37Rv. We demonstrated that persistency of p55TNFR in macrophage cultures increased the synthesis of soluble TNF, p75TNFR and NO, however, had no effects on bacteria killing ability. Furthermore, it did not facilitate enhanced protection to primary acute M. tuberculosis infection in p55^∆NS mice. Without exacerbated lung inflammation, we found a compensatory increase in p75TNFR shedding and decrease in bioactive TNF in BAL of p55^∆NS mice after M. tuberculosis challenge. Defective expressions of CD44 and INFγ attributed to an impaired T cell response during persistent p55TNFR expression that caused marginal transient susceptibility during chronic infection. Moreover, persistent p55TNFR expression induced early reactivation during latent tuberculosis infection. These data indicate a prominent role of p55TNFR shedding in Th1 mediated protection against chronic and latent tuberculosis infection.

• Glypican
• Metalloproteinase
• Shedding

• ADAM17 Protein/metabolism
• Carcinoma, Squamous Cell
• Cell Line, Tumor
• Cell-Derived Microparticles
• Glypicans/metabolism
• Head and Neck Neoplasms
• Humans
• Mass Spectrometry
• Metalloproteases
• Protein Binding
• Proteolysis
• Proteomics/methods
• Squamous Cell Carcinoma of Head and Neck

• ADAM Proteins/metabolism
• ADAM10 Protein
• Amyloid Precursor Protein Secretases/metabolism
• Calcitriol/pharmacology
• Cells, Cultured
• Humans
• Membrane Proteins/metabolism
• Muscle, Smooth, Vascular/drug effects
• Muscle, Smooth, Vascular/metabolism
• Myocytes, Smooth Muscle/drug effects
• Myocytes, Smooth Muscle/metabolism
• Receptors, Tumor Necrosis Factor, Type I/metabolism

• Chemotaxis
• Innate immunity
• Interferon
• Interleukin
• Tumour necrosis factor

• Disability progression
• Primary progressive multiple sclerosis
• Tumor necrosis factor receptor II

• TNFα
• TNFα receptors
• baboon
• fetal inflammatory response syndrome
• sTNFRI
• sTNFRII
• sepsis
• tumor necrosis factor α

• Animals
• Biomarkers/blood
• Female
• Labor Onset/blood
• Papio
• Placental Circulation/physiology
• Pregnancy
• Time Factors
• Tumor Necrosis Factor-alpha/blood

• P40 RR012317 NCRR NIH HHS

• Animals
• Apoptosis
• Carcinoma, Renal Cell/metabolism
• Cell Proliferation
• Disease Models, Animal
• Humans
• Immune System
• Inflammation
• Kidney Diseases/metabolism
• Kidney Diseases/therapy
• Kidney Neoplasms/metabolism
• Kidney Transplantation
• Mice
• Models, Biological
• Protein Structure, Tertiary
• Receptors, Tumor Necrosis Factor, Type I/metabolism
• Receptors, Tumor Necrosis Factor, Type II/metabolism
• Sepsis
• Signal Transduction
• Tumor Necrosis Factor-alpha/metabolism

Tumour necrosis factor-α (TNF-α) has been implicated as an important inflammatory mediator. In vitro, TNF-α is reported to activate human polymorphonuclear neutrophils (PMN), inducing responses such as phagocytic activity, degranulation and oxidative metabolism. Biological responses to TNF-α are initiated by its binding to specific cell surface receptors, and various studies have shown that the major TNF receptor species on PMN is the 75 kDa receptor. To verify the suggestion that the receptor binding domain includes the region close to the N-terminus of the TNF-α molecule, four TNF-α derivatives termed muteins were constructed, using a synthetic cDNA fragment substituting the N-terminal 3–7 selected hydrophilic or hydrophobic amino acids in the original TNF-α genomic DNA. Binding of muteins to PMN was assessed using monoclonal antibodies recognizing either the 55 kDa (p55) or the 75 kDa (p75) TNF receptor subtypes. Blocking by muteins of anti-p75 antibody binding to PMN was as expected from their N-terminal amino acid composition and hydrophilic properties. Hydrophilic muteins competed well with anti-TNF receptor antibodies for binding to the p75 receptor. In contrast, hydrophobic muteins were unable to block anti-p75 binding. Similarly, degranulation, chemiluminescence or enhancement of the PMN response to specific stimuli by the muteins correlated with the hydrophilic properties of the muteins. The significance of these observations in relation to the molecular structure of TNF-α is discussed.

Cytokines are secreted from macrophages and other cells of the immune system in response to pathogens. Additionally, in autoinflammatory diseases cytokine secretion occurs in the absence of pathogenic stimuli. In the case of TRAPS [TNFR (tumour necrosis factor receptor)-associated periodic syndrome], inflammatory episodes result from mutations in the TNFRSF1A gene that encodes TNFR1. This work remains controversial, however, with at least three distinct separate mechanisms of receptor dysfunction having been proposed. Central to these hypotheses are the NF-κB (nuclear factor κB) and MAPK (mitogen-activated protein kinase) families of transcriptional activators that are able to up-regulate expression of a number of genes, including pro-inflammatory cytokines. The present review examines each proposed mechanism of TNFR1 dysfunction, and addresses how these processes might ultimately impact upon cytokine secretion and disease pathophysiology.

• Amniotic Fluid/metabolism
• Amniotic Fluid/microbiology
• Blood Proteins/analysis
• Cell Adhesion Molecules/blood
• Chemokines/blood
• Chorioamnionitis/blood
• Chorioamnionitis/pathology
• Cytokines/blood
• Female
• Humans
• Infant, Newborn
• Infant, Premature/blood
• Matrix Metalloproteinases/blood
• Placenta/metabolism
• Placenta/pathology
• Pregnancy
• Receptors, Vascular Endothelial Growth Factor/blood
• Vascular Endothelial Growth Factor A/blood

• 5U01NS040069-05 NINDS NIH HHS
• U01 NS040069-05 NINDS NIH HHS
• P30 HD018655-28 NICHD NIH HHS
• 5P30HD018655-28 NICHD NIH HHS
• P30 HD018655 NICHD NIH HHS
• U01 NS040069 NINDS NIH HHS

Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status.

Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14), soluble tumour necrosis factor receptor II (sTNFRII) and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6) or diet plus Orlistat (n = 8).

Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8) EU/mL; controls: 3.9(3.2, 5.2) EU/mL, p < 0.001); NAFLD alone produced comparable endotoxin levels to T2DM (NAFLD: T2DM: 10.6(5.6, 14.2) EU/mL; non-diabetic: 10.6(8.5, 15.2) EU/mL), whilst a significant correlation between insulin resistance and serum endotoxin was observed (r = 0.27, p = 0.008). Both sCD14 (p < 0.01) and sTNFRII (p < 0.001) increased with severity of fibrosis. A positive correlation was also noted between sTNFRII and sCD14 in the NAFLD subjects (r = 0.29, p = 0.004).

Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006), weight (p = 0.005) and endotoxin (p = 0.004) compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively.

Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.

• Adolescent
• Adult
• Aged
• Biomarkers/blood
• Emergency Service, Hospital
• Female
• Humans
• Inflammation/blood
• Injury Severity Score
• Interleukin-10/blood
• Interleukin-6/blood
• Leukocyte Elastase/blood
• Male
• Middle Aged
• Respiratory Distress Syndrome/diagnosis
• Respiratory Distress Syndrome/immunology
• Sepsis/diagnosis
• Sepsis/immunology
• Shock, Hemorrhagic/etiology
• Shock, Hemorrhagic/immunology
• Shock, Hemorrhagic/mortality
• Treatment Outcome
• Wounds, Nonpenetrating/complications
• Wounds, Nonpenetrating/immunology
• Wounds, Nonpenetrating/physiopathology