SOMATOSTATIN REGULATION BY CYTOKINES

Inflammatory states are associated with nervous and neuroendocrine responses, which appear to be mediated through the actions of cytokines. Since endotoxin treatment in the rat is associated with declines in thyrotropin (TSH) secretion and growth hormone (GH) secretion, changes that may be explained by stimulation of hypothalamic somatostatin (SRIF), the effects of cytokines on SRIF were examined. In an in vitro model system consisting of fetal rat diencephalic cells interleukin-1 (IL-1), tumor necrosis factor (TNF) and interleukin-6 (IL-6) were found to stimulate the synthesis and release of SRIF. This effect developed slowly over 24 hours and was dose- and time-dependent. Acute release of SRIF over periods up to 1 hour was not found. The mechanism of cytokine stimulation of SRIF is not known. Since the depletion of glial cells in the cultures inhibits the effect, mediators that depend on the presence glia may be involved. The ability of cytokines to stimulate brain SRIF is likely to prove relevant to our understanding in many areas, including brain development, brain responses to injury, and neuroendocrine changes in chronic illness. © 1990.