Infliximab therapy increases the frequency of circulating CD 16 + monocytes and modifies macrophage cytokine response to bacterial infection

Summary Crohn's disease ( CD ) has been correlated with altered macrophage response to microorganisms. Considering the efficacy of infliximab treatment on CD remission, we investigated infliximab effects on circulating monocyte subsets and on macrophage cytokine response to bacteria. Human peripheral blood monocyte‐derived macrophages were obtained from CD patients, treated or not with infliximab. Macrophages were infected with E scherichia coli , E nterococcus faecalis , M ycobacterium avium subsp. paratuberculosis ( MAP ) or M. avium subsp avium , and cytokine levels [tumour necrosis factor ( TNF) and interleukin ( IL) ‐10] were evaluated at different time‐points. To evaluate infliximab‐dependent effects on monocyte subsets, we studied CD 14 and CD 16 expression by peripheral blood monocytes before and after different infliximab administrations. We also investigated TNF secretion by macrophages obtained from CD 16 + and CD 16 − monocytes and the frequency of TNF + cells among CD 16 + and CD 16 − monocyte‐derived macrophages from CD patients. Infliximab treatment resulted in elevated TNF and IL ‐10 macrophage response to bacteria. An infliximab‐dependent increase in the frequency of circulating CD 16 + monocytes (particularly the CD 14 ++ CD 16 + subset) was also observed (before infliximab: 4·65 ± 0·58%; after three administrations: 10·68 ± 2·23%). In response to MAP infection, macrophages obtained from CD 16 + monocytes were higher TNF producers and CD 16 + macrophages from infliximab‐treated CD patients showed increased frequency of TNF + cells. In conclusion, infliximab treatment increased the TNF production of CD macrophages in response to bacteria, which seemed to depend upon enrichment of CD 16 + circulating monocytes, particularly of the CD 14 ++ CD 16 + subset. Infliximab treatment of CD patients also resulted in increased macrophage IL ‐10 production in response to bacteria, suggesting an infliximab‐induced shift to M 2 macrophages.