Disclosures: A.C.W.V., M.E.W., I.A., M.D., A.P.V.: no conflicts of interest; G.dH.: consultant for Centocor, Shire, Teva, BMS, and Glaxo SmithKline; S.V.: Grants/Research Support: UCB; Consultancy: Astra-Zeneca, Ferring, Pfizer, Centocor, MSD; Speakers Bureau: MSD, Abbott, Ferring, UCB; Advisory Committee: Shire, Ferring; P.R.: Grant support, lecture fees, and consulting fees from Abbott, UCB, Centocor, and Schering-Plough; G.vdB.: Grants/research support from MSD, Ferring, and Guiliani; D.W.H.: Grants/research support and is a consultant for Abbott, MSD, UCB, Guiliani, Ferring, Serono, AstraZeneca, Falk, and Tramedico.
Regulatory macrophages induced by infliximab are involved in healing in vivo and in vitro†
Article first published online: 20 SEP 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 3, pages 401–408, March 2012
How to Cite
Vos, A. C. W., Wildenberg, M. E., Arijs, I., Duijvestein, M., Verhaar, A. P., de Hertogh, G., Vermeire, S., Rutgeerts, P., van den Brink, G. R. and Hommes, D. W. (2012), Regulatory macrophages induced by infliximab are involved in healing in vivo and in vitro. Inflamm Bowel Dis, 18: 401–408. doi: 10.1002/ibd.21818
- Issue published online: 13 FEB 2012
- Article first published online: 20 SEP 2011
- Manuscript Accepted: 8 JUN 2011
- Manuscript Received: 31 MAY 2011
- regulatory macrophage;
Regulatory macrophages play an important role in wound healing and gut homeostasis and have antiinflammatory properties. Induction of this cell type (Mψind) by the anti-tumor necrosis factor (TNF) antibodies, infliximab and adalimumab, has recently been shown in vitro. Also, the superiority of infliximab/azathioprine combination therapy over infliximab or azathioprine monotherapy has recently been established, but the mechanism behind this remains unclear. The aim of this study was to examine the induction of regulatory macrophages in patients with and without mucosal healing in response to infliximab. In addition, we studied the effect of infliximab/azathioprine combination treatment on the differentiation and function of regulatory macrophages.
Inflammatory bowel disease (IBD) patients (n = 10) underwent endoscopy before and after first infliximab treatment. Immunohistochemical staining of CD68 and CD206 was performed in all patients. Mixed lymphocyte reactions (MLRs) were treated with infliximab, azathioprine, or both. Macrophage phenotype was evaluated by flow cytometry and inhibition of T-cell proliferation was measured in a secondary MLR containing macrophages and third-party lymphocytes.
A significant induction of regulatory macrophages was observed in patients with mucosal healing after treatment with infliximab; this induction was absent in patients without mucosal healing. In addition, Mψind have the ability to induce wound healing in an in vitro model, further suggesting a key role for infliximab-induced macrophages in mucosal healing. Upon infliximab/azathioprine combination treatment, an increased number of regulatory macrophages was observed. These macrophages also displayed stronger immunosuppressive properties than macrophages induced by infliximab monotherapy.
These data show that regulatory macrophages may be involved in mucosal healing and provide a rationale for the superiority of infliximab/azathioprine combination treatment observed in the clinic. (Inflamm Bowel Dis 2012;)