Changes in the pattern of cytokine production from peripheral blood mononuclear cells in patients with rheumatoid arthritis treated with infliximab and their relation to plasma arginase activity.

Abstract

The aim of this study was to quantify the production of T-cell cytokines from the peripheral blood mononuclear cells (PBMCs) of RA patients before and after treatment with anti-tumor necrosis factor (TNF)-α infliximab (IFX). We stimulated the PBMCs of RA patients (n = 24) in vitro and quantified the cytokines in the culture supernatant using enzyme-linked immunosorbent assay. Unexpectedly, the cytokines tested, interferon (IFN)-γ, interleukin (IL)-4 and IL-17, were all found to have increased, rather than decreased, after the treatment. When the patients were divided into two groups according to the plasma activity of arginase, which is implicated in the immune-suppressive function of myeloid-derived suppressor cells, the substantial increase in the cytokine production ex vivo was only detected in the group in which the arginase activity was decreased after the treatment with IFX. In fact, although the ex vivo production of IL-21 increased along with the other cytokines, the plasma concentration of IL-21 decreased significantly after IFX treatment. It is important to exercise caution in interpreting ex vivo cytokine production data, in that they can be negatively influenced by the immune-suppressive mechanisms that prevent excessive inflammation. Thus, to analyze the T-cell response accurately, T-cell markers that are detectable in the serum or plasma need to be discovered. The concentrations of IFN-γ, IL-4 and IL-17 were all below detection limits, but that of IL-21 was detectable in the plasma and inversely correlated with the production of IL-21 ex vivo. This may indicate the involvement of Th17 response in the pathogenesis of RA.