SUMMARYTransforming growth factor-b (TGF-b ) is an inhibitory cytokine recognized as a key regulator of immunological homeostasis and inflammatory responses. TGF-b is involved in experimental models of oral tolerance and in the pathogenesis of experimental colitis. Patients with inflammatory bowel disease (IBD) have inappropriate T cell responses to antigenic components of their own intestinal microflora, suggesting the presence of a disorder in the normal mucosal immune mechanism that ensures the downregulation of responses to harmless constituents in the microflora. To evaluate the contribution of TGFb to this imbalance, we measured TGF-b 1 production by lamina propria mononuclear cells (LPMC) and T cells isolated from tissue specimens of patients with Crohn's disease (CD), ulcerative colitis (UC) and controls. Cells were cultured in the presence or absence of anti-CD2 plus anti-CD28 MoAbs and TGFb 1 production in culture supernatants was measured by ELISA. LPMC isolated from CD patients produced significantly less TGF-b 1 than controls when stimulated via CD2 plus CD28 pathways ( P = 0·001)] conversely, in UC patients increased production of TGF-b 1 compared to controls was observed ( P = 0·0005). These differences were also observed with purified lamina propria (LP) T cells in both diseases and were associated with the presence of inflammation. Thus, TGF-b 1 production shows contrasting secretion in CD and in UC, probably as a consequence of the different Th polarization. The absolute or relative defect in TGF-b 1 production observed in CD and UC may contribute to the perpetuation of inflammation.

Background and aims: Cholera toxin B subunit (CT-B) is a powerful modulator of immune responses. The authors have previously demonstrated that oral administration of recombinant CT-B (rCT-B) is able to prevent and cure the Crohn's disease (CD)-like trinitrobenzene sulfonic acid (TNBS) mediated colitis. In this study they extended their observations and examined if rCT-B interferes with the molecular signaling underlying the Th1 type response both in TNBS colitis and in ex vivo human CD explants. Methods: TNBS treated mice were fed with rCT-B, and IFN-c and IL-12 production by colonic lamina propria mononuclear cells (LPMC) was examined by ELISA. In vitro culture of mucosal explants from CD patients and non-inflammatory bowel disease controls, pre-incubated with rCT-B, were examined for IFNc and IL-12 production by ELISA and semiquantitative reverse transcription polymerase chain reactions. STAT-1, -4, -6 activation and T-bet expression were examined following rCT-B treatment by western blotting both in TNBS treated mice and in human mucosal explants. Conclusions: These studies indicate that CT-B inhibits mucosal Th1 cell signaling and suggest that rCT-B may be a promising candidate for CD therapy.