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-lprfas 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.