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

Abstract

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-1beta, 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.

Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis

“…This growth factor was shown, for example, to play an important role in the differentiation (22,40) and survival (41,42) of oligodendrocytes and to be beneficial in the treatment of EAE (43,44). It seems reasonable to assume that the IGF-I produced by MG is responsible, at least in part, for the shift to a Th2 phenotype (45) and thus for the increased number of MHC class II + MG as well as of the newly formed BrdU + /MHC class II + MG expressing IGF-I. The increased oligodendrogenesis was found to correlate with a higher incidence of newly formed MHC class II + MG.…”

Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin-like growth factor-1-mediated interleukin-10 production

“…6a,b). Kooijman et al [23] reported that IGF-1 could stimulate IL-10, an important anti-inflammatory cytokine, production by activated normal human T cells. We hypothesized that the increased miR-223 levels could suppress IGF-1R expression, leading to impaired IL-10 production upon IGF-1 stimulation in RA T cells.…”

Regulation of interleukin-8 expression in human prostate cancer cells by insulin-like growth factor-I and inflammatory cytokines

“…It stimulates TNFa, IL-8 and IL-6 secretion in human monocytes [9][10][11], IL-10 expression in T cells [12], and the production of interferon-c and IL-6 in neonatal mononuclear cells [13]. Since cytokines in the tumour microenvironment strongly influence cancer pathogenesis, a more detailed understanding of the regulatory mechanisms leading to cytokine expression in tumour cells may provide new opportunities to treat cancer.…”