Differential effects of the tumor necrosis factor alpha-blocker infliximab and etanercept on immunocompetent cells in vitro

Abstract: The tumor necrosis factor-alpha (TNFα) antagonists infliximab or etanercept are used in the management of chronic inflammatory disorders but have differences in clinical activity. Here we show that both have different effects on immunocompetent cells in vitro. Peripheral blood mononuclear cells (PBMC) from 20 healthy donors were incubated with infliximab or etanercept alone and in a co-culture with recall-antigens (BCG, tetanus toxoid [TT]). Expression of the activation marker CD69 on different PBMC-subpopulations was determined by flow cytometry, release of Th1-, Th2- and macrophage/monocyte-related cytokines into the supernatants by ELISA. There were strong inter-individual differences in reactivity of PBMC of the 20 donors towards infliximab and etanercept. On the whole group level, both enhanced IL-10 production but had opposite effects on the TNFα- and IFNγ-secretion; Th2-cytokine-secretion (IL-13, IL-5) was differentially influenced. IL-13 production was significantly reduced by infliximab but not by etanercept. IL-5 secretion was strongly enhanced in individual subjects but was not significantly influenced on the whole group level. Etanercept but not infliximab significantly decreased the CD69-expression by CD8+ T- and CD56+ natural killer(NK)-cells. Co-culture with recall antigens enhanced most of these reactions. Our data indicate that individual predisposition and immunological reactivity may be an important factor influencing the therapeutic efficacy of anti-TNFα agents. [Copyright &y& Elsevier]