Interleukin-11 Modulates Th1/Th2 Cytokine Production from Activated CD4 + T Cells

Abstract

Recombinant human interleukin-11 (rHuIL-11) is a pleiotropic cytokine with effects on multiple cell types. rHuIL-11 reduces activated macrophage activity and downregulates production of proinflammatory mediators, such as tumor necrosis factor-α (TNF-α) and nitric oxide (NO). In vitro and in vivo, rHuIL-11 inhibits production of key immunostimulatory cytokines, including IL-12 and interferon-γ (IFN-γ). rHuIL-11 has recently demonstrated immunomodulatory activity to downregulate IFN-γ production, increase IL-4 production, and reduce inflammatory tissue injury in a human psoriasis clinical trial. The cellular mechanisms of these effects are not fully elucidated. We demonstrate here that expression of gp130 and IL-11 receptor (IL-11R) α mRNA, components of the IL-11R complex, are detected in human 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 differentiation, rHuIL-11 acts to inhibit IL-2 production as well as IL-12-induced IFN-γ 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 through which rHuIL-11 may ameliorate such inflammatory diseases as psoriasis.