In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment.

Summary Background : Adalimumab, a fully human monoclonal antibody to tumour necrosis factor, was recently introduced for therapy of Crohn's disease. Aim : Since induction of apoptosis of inflammatory cells is thought to be an important mechanism of action of the antitumour necrosis factor monoclonal antibody infliximab, we studied the induction of apoptosis of activated peripheral blood monocytes by adalimumab. Method : Apoptosis was analysed at the levels of the cell membrane, mitochondria and DNA by flow cytometry. Results: We found that both adalimumab and infliximab induced apoptosis in cultured monocytes, while etanercept did not. Apoptosis induction was caspase‐dependent and detectable already after 2 h. The production of interleukin‐10 and interleukin‐12 by monocytes was down‐regulated significantly by adalimumab and infliximab but not by etanercept, while levels of soluble tumour necrosis factor in monocyte cultures were down‐regulated by all three reagents. Conclusions : These data show that both adalimumab and infliximab affect monocyte cytokine production and induce apoptosis of activated monocytes. Our findings will have to be further correlated to therapeutic efficacy of these antitumour necrosis factor reagents.

CD28-B7 interaction plays a critical costimulatory role in inducing T cell activation, while CTLA-4-B7 interaction provides a negative signal that is essential in immune homeostasis. Transfer of CD45RBhighCD4+ T cells from syngeneic mice induces transmural colon inflammation in SCID recipients. This adoptive transfer model was used to investigate the contribution of B7-CD28/CTLA-4 interactions to the control of intestinal inflammation. CD45RBhighCD4+ cells from CD28−/− mice failed to induce mucosal inflammation in SCID recipients. Administration of anti-B7.1 (but not anti-B7.2) after transfer of wild-type CD45RBhighCD4+ cells also prevented wasting disease with colitis, abrogated leukocyte infiltration, and reduced production of proinflammatory cytokines IL-2 and IFN-γ by lamina propria CD4+ cells. In contrast, anti-CTLA-4 treatment led to deterioration of disease, to more severe inflammation, and to enhanced production of proinflammatory cytokines. Of note, CD25+CD4+ cells from CD28−/− mice similar to those from the wild-type mice were efficient to prevent intestinal mucosal inflammation induced by the wild-type CD45RBhigh cells. The inhibitory functions of these regulatory T cells were effectively blocked by anti-CTLA-4. These data show that the B7-CD28 costimulatory pathway is required for induction of effector T cells and for intestinal mucosal inflammation, while the regulatory T cells function in a CD28-independent way. CTLA-4 signaling plays a key role in maintaining mucosal lymphocyte tolerance, most likely by activating the regulatory T cells.

No abstract

No abstract