Differential effect of corticotropin releasing factor on interleukin-lα and interleukin-lβ-induced prostaglandin synthesis in endothelial cells and fibroblasts

The inflammatory response involves two major pathways: one comprises the immune response, predominantly mediated by cytokines such as interleukin 1 (IL-1). The other pathway involves neuroendocrine mechanisms, the most significant of which consists of stimulation of the hypothalamic-pituitary-adrenal axis (HPA). Activation of the neuroendocrine axis results in corticotropin releasing factor (CRF) release, followed by enhancement of plasma levels of adrenocorticotropic hormone (ACTH) and finally increased production of glucocorticoids by the adrenal cortex. There is increasing evidence for tight connections between both pathways. Thus, it has become evident that IL-1 stimulates the HPA axis by inducing CRF release from the hypothalamus. Cytokines are very potent modulators of cell function, and IL-1 is known to induce prostaglandin (PG) production by many cells, including endothelium and fibroblasts. Additional evidence suggests that not only the end product of the HPA axis, the glucocorticoids, but also other hormones, primarily CRF, might be involved in the regulation of the inflammatory response. CRF has been identified in a number of peripheral sites such as the heart, spleen, adrenal and lung. Recently we discovered a novel neuroimmune mechanism whereby CRF regulates IL-1α-induced PG synthesis in fibroblasts and endothelial cells.7 Presently we compared the effect of CRF on IL-1α and IL-1β-induced PG synthesis.