Interleukin-1 beta stimulates somatostatin biosynthesis in primary cultures of fetal rat brain.

Interleukin-1 (IL-1), a secretory product of activated macrophages and many other cell types, is an important mediator of the acute phase reaction to infection and to endotoxin administration. Previous reports that GH and TSH secretion are decreased following injection of endotoxin or IL-1 led us to test the hypothesis that IL-1 acts by releasing increased amounts of somatostatin (SS), a hypothalamic factor inhibitory of both GH and TSH release. Primary cultures of dispersed fetal rat diencephalic cells were found to contain increasing amounts of immunoreactive SS in both cells and media after addition of recombinant human IL-1 beta. This increase was detectable at 24 hours and continued for up to 6 days, the longest time interval tested. Increased content of SS peptide was accompanied by marked increases in SS mRNA. These changes were dose-related, the lowest effective dose being 10(-10) M. In contrast to the long term response, exposure of the cells to IL-1 beta for one hour had only minimal stimulating effects on somatostatin release. These data indicate that IL-1 beta is neurotrophic for the somatostatinergic neuron, an action that may be responsible at least in part, for the neuroendocrine response to infection.