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Originally published online as doi:10.1189/jlb.0404248 on July 26, 2004

Published online before print July 26, 2004
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(Journal of Leukocyte Biology. 2004;76:862-867.)
© 2004 by Society for Leukocyte Biology

Insulin-like growth factor-I stimulates IL-10 production in human T cells

Ron Kooijman1 and Astrid Coppens

Laboratory for Neuroendocrine Immunology, Department of Pharmacology, Medical School, Free University of Brussels (VUB), Belgium

1 Correspondence: Department of Pharmacology, Medical School, Free University of Brussels (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium. E-mail: rkooi{at}farc.vub.ac.be

There is vast body of evidence that the insulin-like growth factor (IGF)-I exerts immunomodulatory effects in vitro and in vivo. In vitro studies indicate that stimulatory effects of IGF-I may be exerted through augmentation of inflammatory cytokine production. To further explore the immunomodulatory effects of IGF-I through regulation of cytokine production, we tested the in vitro effects of IGF-I on the secretion of inflammatory T helper cell type 1 (Th1) and Th2 cytokines by human peripheral blood mononuclear cells (PBMC). To this end, PBMC were stimulated with the T cell mitogen phytohemagglutinin (PHA), and cytokines in the culture media were assessed after 18, 42, 66, and 80 h of culture. We found that IGF-I stimulated the secretion of the Th2 cytokine interleukin (IL)-10 by 40–70% in PHA-stimulated PBMC. In addition, we observed a small stimulatory effect (15%) on the secretion of another Th2 cytokine IL-4. The secretion of IL-2, IL-5, IL-6, interferon-{gamma}, and the inflammatory cytokines IL-1ß, IL-8, and tumor necrosis factor {alpha} was not or was hardly affected. IL-10 secretion was also stimulated in purified T cells, and we established that IGF-I also stimulated IL-10 mRNA expression by 100–150%. The monocyte-activating bacterial cell-wall product lipopolysaccharide induced IL-10 production in PBMC, but this was not affected by IGF-I. As IL-10 predominantly exerts anti-inflammatory actions and suppresses Th1-dependent immune responses, our results indicate that IGF-I may exert inhibitory actions on inflammatory and Th1-mediated cellular immune responses through stimulation of IL-10 production in T cells.

Key Words: leukocytes • cytokines • inflammation • Th1 • Th2




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