Interleukin-11 modulates Th1/Th2 cytokine production from activated CD4(+)T cells

Recombinant human interleukin-11 (rHuIL-11) is a pleiotropic cytokine with effects on multiple cell types. rHuIL-11 reduces activated macrophage activ ity and downregulates production of proinflammatory mediators, such as tumo r necrosis factor-alpha (TNF-alpha) and nitric oxide (NO). In vitro and in vivo, rHuIL-11 inhibits production of key immunostimulatory cytokines, incl uding IL-12 and interferon-gamma (IFN-gamma). rHuIL-11 has recently demonst rated immunomodulatory activity to downregulate IFN-gamma production, incre ase IL-4 production, and reduce inflammatory tissue injury in a human psori asis clinical trial. The cellular mechanisms of these effects are not fully elucidated. We demonstrate here that expression of gp130 and IL-11 recepto r (IL-11R) alpha mRNA, components of the IL-11R complex, are detected in hu man and murine CD4(+) and CD8(+) lymphocytes, suggesting that rHuIL-11 can directly interact with T cells. In a cell culture model of murine T cell di fferentiation, rHuIL-11 acts to inhibit IL-2 production as well as IL-12-in duced IFN-gamma production and enhances IL-4 and IL-10 production. rHuIL-11 had no effect on T cell proliferation. The ability of rHuIL-11 to modulate cytokine production from activated CD4(+) T cells provides a mechanism thr ough which rHuIL-11 may ameliorate such inflammatory diseases as psoriasis.