Infliximab induces potent anti-inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn's disease

Background: Anti-TNF alpha therapy with infliximab is effective for Crohn's disease. Infliximab neutralizes the biological activities of TNF alpha, a cytokine involved in host-defence against certain infections. Aim: To evaluate the effects of infliximab on the gut and peripheral immune system functions. Methods: Biopsies and blood samples from three clinical trials of inflixima b in Crohn's disease were analysed. Pharmacokinetics, changes in leucocyte counts and T cell subsets, T cell function, and cytokine profiles of lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (P BMC) were analysed. Results: Infliximab has a serum half-life of 9.5 days and is still detectab le in serum 8 weeks after infusion. Leucocyte counts showed consistent chan ges from baseline toward normal values after therapy. Monocytes and lymphoc ytes were modestly increased, while neutrophils were decreased 4 weeks afte r treatment. Lymphocyte subsets and T cell proliferative responses were not altered after therapy. The proportion of PBMCs capable of producing IFN ga mma, and TNF alpha did not change, while Th1 cytokine production by stimula ted LPMC was decreased after infliximab therapy. Conclusion: The clinical efficacy of infliximab is based on local anti-infl ammatory and immunomodulatory effects in the bowel mucosa, without generali zed suppression of systemic immune functions in Crohn's disease patients.