Psychoneuroimmunology of Interleukin-10

Appropriate interactions between the neuroendocrine and immune systems are important for optimal host defense and homeostasis. Pro-inflammatory cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha, arising from disease processes, can activate the hypothalamic-pituitary-adrenal (HPA) axis. Interleukin-10, as a prominent anti-inflammatory cytokine in the immune system, has been shown to be expressed in both the central nervous system and neuroendocrine system. Little is known, however, about IL-10's functions in the HPA axis. We hypothesize that IL-10 contributes to the homeostasis of the HPA axis. In order to examine this hypothesis, we conducted in vitro and in vivo experiments. In our in vitro studies, we found the following: IL-10 induces the production of corticotropin-releasing hormone (CRH) from the hypothalamus; IL-10 induces the production of adrenocorticotropic hormone (ACTH) from AtT-20 cells derived from pituitary; and IL-10 inhibits glucocorticoid (GCS) production in Y-1 cells in the presence of ACTH. In our in vivo studies, we found that serum corticosterone in IL-10 knockout mice is significantly higher than in wild type mice under basal conditions and following immune and physiologic stress. In our microarry analysis, we determined gene expression profiles regulated by IL-10 and interferon (IFN)-gamma in cells derived from the HPA axis. The results showed that quorums of genes are modulated by IL-10 and IFN-gamma in these neuroendocrine cells, which provides a valuable repository to aid in understanding cytokine functions in the HPA axis at the molecular level. In addition, we found that endogenous IL-10 contributes to pain behavior in response to a noxious thermal stimulus as well as Capsaicin induced pain behaviors. Moreover, we found that cytokines such as IFN-¦Ã and IL-10 are able to regulate indoleamine 2, 3-dioxygenase (IDO) expression in cells of hypothalamic and pituitary origin. The capability of IL-10 to suppress IFN-¦Ã induced IDO expression implies that IL-10 has a putative neuroprotective role in the HPA axis. These novel data strongly suggest that IL-10 plays a potential role in the homeostasis of the HPA axis and has a complicated role in pain perception.