Interleukin-11 induces Th2 polarization of human CD4(+) T cells

Exploration of the immunomodulatory activities of the multifunctional cytok ine interleukin-11 (IL-11) has prompted several therapeutic applications. T he immunomodulatory effects of IL-11 on human antigen-presenting cells and on T cells were investigated. IL-11 inhibited IL-12 production by activated CD14(+) monocytes, but not by mature dendritic cells (DCs) stimulated via CD40 ligation. Moreover, IL-11 did not affect either DC maturation, as demo nstrated by phenotypic analysis and evaluation of cytokine production, or D C generation from progenitor cells in the presence of specific growth facto rs. Molecular analysis demonstrated the expression of IL-11 receptor messen ger RNA in highly purified CD14(+) monocytes, CD19(+) B cells, CD8(+), and CD4(+) T cells, and CD4(+) CD45RA(+) naive T lymphocytes, in keeping with t his finding, IL-11 directly prevented Th1 polarization of highly purified C D4(+)CD45RA(+) naive T cells stimulated with anti-CD3/ CD28 antibodies, as demonstrated by significant increases of IL-4 and IL-5, by significantly de creased interferon-gamma production and by flow cytometry intracellular sta ining of cytokines. Coincubation of naive T cells with DCs, the most potent stimulators of Th1 differentiation, did not revert IL-11-mediated Th2 pola rization. Furthermore, parallel experiments demonstrated that the activity of IL-11 was comparable with that induced by IL-4, the most effective Th2-p olarizing cytokine. Taken together, these findings show that IL-11 inhibits Th1 polarization by exerting a direct effect on human T lymphocytes and by reducing IL-12 production by macrophages. Conversely, IL-11 does not exert any activity on DCs. This suggests that IL-11 could have therapeutic poten tial for diseases where Th1 responses play a dominant pathogenic role. (Blo od. 2001;97:2758-2763) (C) 2001 by The American Society of Hematology.