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

Abstract

Background: Anti-TNFα therapy with infliximab is effective for Crohn's disease. Infliximab neutralizes the biological activities of TNFα, 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 infliximab 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 (PBMC) were analysed. Results: Infliximab has a serum half-life of 9.5 days and is still detectable in serum 8 weeks after infusion. Leucocyte counts showed consistent changes from baseline toward normal values after therapy. Monocytes and lymphocytes were modestly increased, while neutrophils were decreased 4 weeks after treatment. Lymphocyte subsets and T cell proliferative responses were not altered after therapy. The proportion of PBMCs capable of producing IFNγ and TNFα did not change, while Th1 cytokine production by stimulated LPMC was decreased after infliximab therapy. Conclusion: The clinical efficacy of infliximab is based on local anti-inflammatory and immunomodulatory effects in the bowel mucosa, without generalized suppression of systemic immune functions in Crohn's disease patients.