What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

Table 2 Principal findings on inflammatory cytokines in irritable bowel syndrome in humans, and in in vitro and animal models

Principal findings
TNF-α
Animal: D-IBS supernatants have ↑ levels of proinflammatory cytokines and they cause hypersensitivity in mouse colonic afferent endings[122]
Human: IBS has ↑ circulating TNF-α levels[109,112], especially D-IBS[112] or in patients with comorbidities such as fibromyalgia, premenstrual dysmorphic disorder and chronic fatigue syndrome[109]. Baseline and LPS-stimulated levels in PBMCs of proinflammatory cytokines as TNF-α, in IBD and D-IBS, are ↑ and are related to symptom intensity[108]. TLR-2, TLR-4 and TLR-5 antagonists induce TNF-α production[128]. No difference in TNF-α and other proinflammatory cytokine production (IL-6 and IL-1β) in the gut of IBS subjects compared to controls[116]
IL-6
In vitro: No differences in colonic production between IBS and controls 116. IL-6 have excitatory action on colonic cells from IBS rats producing neuronal activation and absorption/secretory responses[115]
Animal: IL-6 colonic secretion is ↑ in IBS rats and activate submucosal neurons[127]
Human: IL-6 blood levels are ↑ in all IBS subtypes[109-111]. IL-6 levels are related to ACTH response and ∆ACTH/∆Cortisol ratio[110]. Baseline and LPS or TLR agonist-stimulated PBMC levels are ↑ in IBS[108]
IL-8
In vitro: Reduced expression of mRNA of IL-8 in ex vivo biopsy cultures[116]
Human: Circulating levels of IL-8 are ↑ in IBS[109-111,119]. TLR-3 and TLR-7 agonists induce IL-8 production in PBMCs[128]
IL-1β
Animal: In stressed rats with previous acute colitis IL-1β mRNA expression is ↓[117]
Human: ↑ IL-1β levels in IBS[108,128], in C-IBS and in D-IBS[108]. With TNF-α, IL-1β↑ levels are found in IBS subjects with fibromyalgia, premenstrual dysmorphic disorder and chronic fatigue syndrome[109]. IL-1β↑ production in PBMCs stimulated by antiCD3/CD28 antibody[91] and by TLR-4 and TLR-5 agonists[128]. Increased IL-1β expression in rectum of PI-IBS[121]
TGF-1β
Animal: No different expression of TGF-β1 protein in colon of IBS rats[11]
Human: TGF-1β intermediate producers may be at risk of developing IBS[114]
IL-10
Human: IBS subjects have ↓ circulating levels of IL-10[112]. Altered IL-10/IL-12 ratio in PBMCs with Th1 proinflammatory state[113]. IL-10 levels are ↓ and IFNγ levels are ↑ in colon of PI-IBS compared to non PI-IBS and controls[119]. IL-10 high producer genotype is protective against IBS[114]
Th2 cytokines (IL-4, IL-5, IL-13)
Animal: Th2 cytokines may have a role in intestinal hypercontractility[123]
Human: Stimulated PBMCs IL-5 and IL-13 levels are ↑ in IBS[124]

TNF-α: Tumor necrosis factor α; D-IBS: Diarrhoea-predominant irritable bowel disease (IBS); IBD: Inflammatory bowel disease; LPS: Lipopolysaccharide; PBMCs: Peripheral blood mononuclear cells; TLR: Toll like receptor; IL: Interleukin; ACTH: Adrenocorticotropic hormone; C-IBS: Constipation-predominant IBS; PI-IBS: Post-infectious IBS; TGF-1β: Tumor growth factor 1 β; IFNγ: Interferon γ; Th2: T-cell mediated helper response.