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 activity and downregulates production of proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO). In vitro and in vivo, rHuIL-11 inhibits production of key immunostimulatory cytokines, including IL-12 and interferon-gamma (IFN-gamma). rHuIL-11 has recently demonstrated immunomodulatory activity to downregulate IFN-gamma 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) alpha 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-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 through which rHuIL-11 may ameliorate such inflammatory diseases as psoriasis.
Bozza
M
M
Department of Molecular Medicine, Genetics Institute, Andover, MA 01810, USA.
Bliss
J L
JL
Dorner
A J
AJ
Trepicchio
W L
WL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016764:Cell Polarity / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017370:Interleukin-11 / Q000378:metabolism / Q000502:physiology*; D053703:Interleukin-11 Receptor alpha Subunit; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; C508428:IL11RA protein, human; C508429:Il11ra1 protein, mouse; C508431:Il11ra2 protein, mouse; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma