Effects of Anti-Cytokine Antibodies on Gut Barrier Function

Table 3

Direct or indirect evidence of anti-cytokine antibodies acting on gut barrier function.

Anti-cytokine antibodies	Subjects	Effects of anti-cytokine antibodies	Ref
Ani-TNF Ab	SAMP1/YitFc mouse model with ileitis	(i) Downregulated epithelial apoptosis; (ii) Decreased membrane bound Fas/CD95 expression; (iii) Increased lamina propria mononuclear cell apoptosis	[28]
	Rat model of indomethacin-induced enterocolitis	(i) Prelesion administration of infliximab markedly reduced the intestinal permeability; (ii) No obvious microscopic or macroscopic alterations	[29]
	Rat model of indomethacin-induced enterocolitis	(i) Alleviated small bowel inflammation partially due to improvement of increased intestinal permeability	[30]
	CD patients	(i) Increased intestinal permeability observed in patients before treatment has significantly reduced to levels within normal range	[25, 26, 144]
	Enteric biopsies of CD patients	(i) Reduced epithelial apoptosis; (ii) Improved transepithelial electrical resistance	[27]
Anti-IL-6R Ab	SW480 cells	(i) Reversed the increased clonogenicity and invasiveness of SW480 cells induced by IL-6; (ii) Inhibited the release of invasion linked MMP-9 and MMP-2	[55]
	Mouse model of T cell transfer-induced colitis	(i) Reduced colitis score as comparing with the control group; (ii) Reduced colonic mRNA levels of IFN-γ, TNF-α, and IL-1β; (iii) Suppressed intercellular expressions of ICAM1 and VCAM1 in colonic vascular endothelial cells	[56]
	Mouse model of T cell transfer-induced colitis	(i) Reduced level of colitis; (ii) Diminished leukocyte recruitment; (iii) Increased T cell apoptosis	[57]
	CD patients	(i) An 80% therapeutic response was observed as compared with 30% response from the placebo group; (ii) No obvious effect on mucosal healing	[54]
Anti-IL-6 Ab	Mouse model with ethanol- and burn-induced injury	(i) Reduced morphological changes in the ileum; (ii) Decreased bacterial translocation to the mesenteric lymph node; (iii) Reduced myosin light chain phosphorylation in intestinal epithelial cells; (iv) Maintained ZO-1 and occludin localisation with actin	[58]
	Mouse sepsis model induced by caecal ligation and a puncture method	(i) Reduced serum productions of IL-6 and IL-10; (ii) Reduced colonic production of TNF-α; (iii) Alleviated upregulation in mRNA expressions of E-cadherin and desmoglein-2	[59]
	Mouse model of DSS-induced colitis	(i) Reduced mucosal damages; (ii) Decreased inflammatory infiltrates; (iii) Improved intestinal permeability; (iv) Suppressed expressions of claudin-2 and myosin light chain kinase	[71]
Anti-IL-12 Ab	IL-10-deficient mouse model of colitis	(i) Reduced colitis; (ii) Reduced mesenteric lymph node and colonic CD4+ T cells; (iii) Reduced IFN-γ producing T cells in the mesenteric lymph node	[77]
	Mouse model of TNBS-induced colitis	(i) Improved clinical and histological features of colitis; (ii) Inability for lamina propria CD4+ T cells to secrete IFN-γ upon in vitro stimulation	[78]
	MRL/MpJ-lpr^fas mice and SJL/J mice with TNBS colitis	(i) Anti-IL-12 antibody induced T cell apoptosis through Fas pathway	[79]
	CD patients	(i) Decreased productions of IL-12, IFN-γ, and TNF-α in colonic lamina propria mononuclear cells; (ii) No significant difference in the remission rate was observed between the treatment group and the placebo group	[80]
Anti-IL-23 Ab	Mouse model of TNBS-induced colitis	(i) Reduced colitis; (ii) Restored downregulation of claudin-8 in colonic mucosa	[82]
	CD patients	(i) Higher remission rate as compared with the placebo group; (ii) Reduced levels of biomarkers C-reactive protein and faecal calprotectin	[88]
	Enteric biopsies of CD patients	(i) Decreased colonic expression of genes associated with the IL-23/IL-17 axis such as IL-23, IL-26, and IL-17A	[89]
Anti-p40-Ab	CD patients	(i) Induced clinical response	[90, 91]
Anti-IL-17 Ab	Mouse model of DSS-induced colitis	Anti-IL-17 Ab; (i) Increased mucosal mRNA levels of TNF-α, IFN-γ, IL-6, RANTES, and IP-10	[103]
	Mouse model of DSS-induced colitis	Pretreatment with anti-IL-17F Ab; (i) Suppressed inflammation induced caecal edema and colonic shortening	[145]
	Multidrug resistance mouse model of colitis	Inhibition with anti-IL-17A or anti-IL-17RA Ab; (i) Promoted colitis exacerbation; (ii) Severe weakening of the intestinal epithelial barrier; (iii) Enhanced colonic inflammation	[104]
	Mouse model of T cell transfer-induced colitis	Coinhibition with anti-IL-17A and IL-17F Ab; (i) Reduced intestinal inflammation	[105]
	CD patients	Inhibition with anti-IL-17A Ab; (i) Adverse events; (ii) Elevated inflammatory markers including C-reactive protein and faecal calprotectin	[107]

Ab: antibody; CD: Crohn’s disease; IL: interleukin; MMP: matrix metalloproteinase; VCAM: vascular cell adhesion molecule; ICAM: intercellular adhesion molecule; IFN: interferon; IP-10: IFN-γ-induced protein-10; TNF: tumor necrosis factor; ZO: zonula occluden; STAT: signal transducer and activator of transcription; HLA: human leukocyte antigen.