Comparison of In Vitro and In Vivo Effects of Infliximab on Cytokine Production in Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis

Objectives. To clarify in vitro and in vivo effects of tumor necrosis factor-alpha (TNF-alpha) blocker, infliximab, on cytokine production in proliferating CD4+ T cells in patients with rheumatoid arthritis (RA). Methods. Peripheral blood mononuclear cells (PBMCs), separated from patients with RA (n=22) and normal person (n=22), were labeled with CFSE [5 (and 6) carboxyfluorescein diacetate, succinimidyl ester], and cultured with ConA. Cytokine production of IFN-gamma, IL-4 and TNF-alpha in proliferating CD4+ T cells was analyzed by flow cytometry. In vivo effects of infliximab on CD4+ T cells were serially analyzed in active RA patients (n=10). In vitro effects on CD4+ T cells were also examined in culture with infliximab. Results: In the analysis of in vivo, treatment with infliximab augmented IFN-gamma and IL-4 production in proliferating CD4+ T cells and reduced proliferation (p<0.05). In vitro infliximab decreased proliferation, IFN-gamma and TNF-alpha production, and increased IL-4 production in proliferating CD4+ T cells. Conclusions: TNF-alpha blockers altered in vitro and in vivo cytokine production in proliferating CD4+ T cells in patients with RA. Although in vitro and in vivo effects of CD4+ T cells by the drug were not directly linked, clarification of the difference between them is important to understand the mechanism of antiinflammatory drugs in vivo and in vitro in RA patients.