Lessons for human inflammatory bowel disease from experimental models

A preferential p110α/γ PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-κB-dependent manner

“…Furthermore, it is noteworthy that wortmannin has been shown to ameliorate murine colitis, at least in part, due to inhibition of production of TNF-␣ (28). Anti-inflammatory cytokines (e.g., IL-10) have been shown to play a critical role in preventing colitis (5). Interestingly, under in vitro conditions, PIK-75 markedly inhibited the induced production of IL-10 from hPBMCs stimulated using a combination of anti-CD3 and anti-CD28 MAbs (IC 50 : 0.007 M; Supplemental Fig.…”

Tripterygium glycosides suppress production of interleukin‐4 by splenocytes in oxazolone‐induced murine colitis

“…Studies of experimental enteritis in animal models using antigens or haptens (dinitrobenzene sulfonic acid, trinitrobenzene sulfonic acid, dextran sulphate sodium, OXZ) provide scientific evidence for the pathogenesis of IBD, and lay a solid foundation for manufacturing new drugs or devising new therapeutic regimes. 4,5 It has been reported that pathological lesions in OXZinduced murine colitis are similar to that in human ulcerative colitis. 2 In studies using molecular biology and immunology techniques it has been found that the murine model of IBD was Th2-response predominant and was characterized by an overproduction of IL-4 (which indicated that a Th2-predominant immunological response might be involved in the pathogenesis of ulcerative colitis).…”

“…Studies of experimental enteritis in animal models using antigens or haptens (dinitrobenzene sulfonic acid, trinitrobenzene sulfonic acid, dextran sulphate sodium, OXZ) provide scientific evidence for the pathogenesis of IBD, and lay a solid foundation for manufacturing new drugs or devising new therapeutic regimes 4,5 …”

FR167653, a potent suppressant of interleukin‐1 and tumor necrosis factor‐α production, ameliorates colonic lesions in experimentally induced acute colitis1

“…Mesenchymal cells have been involved in the production of IL‐1β, IL‐6 and TNF‐α when exposed to adequate inflammatory stimuli 28 . However, overwhelming evidence supports a major role of activated mucosal immune cells for the production of inflammatory cytokines in IBD 3,4,20–22 . In acute stages of IBD, neutrophils predominate in the colonic inflammatory infiltrate.…”

“…Cytokines are pleiotropic inflammatory mediators that are active in fentomolar concentrations, and their production is closely regulated 2 . As part of the T helper (Th) 1 group of cytokines, IL‐1α, IL‐1β, and TNF‐α are known to amplify the immunological response in the gut by activating immune, mesenchymal and epithelial cells, and simultaneously inducing the production in cascade of other cytokines, arachidonic acid metabolites, and proteases from inflamed tissue 1,3,4 . Moreover, IL‐1β and TNF‐α, when administered in high concentrations, are able to induce intestinal damage 1 …”