Alpha-MSH and gamma-MSH modulate early release of hypothalamic PGE2 and NO induced by IL-1beta differently.

Interleukin-1beta (IL-1beta) stimulates corticotropin-releasing hormone (CRH) secretion in hypothalamus, which involves the release of prostaglandins (PGE2) and nitric oxide (NO). We have demonstrated that melanocortins can inhibit the early effects of IL-1beta on the HPA axis by acting on the central nervous system (CNS). Our study investigated whether alpha-melanocyte stimulating hormone (alpha-MSH) and gamma-MSH could inhibit IL-1beta-induced PGE2 and NO release in hypothalamus in the rapid activation of the HPA axis. An i.c.v. injection of 12.5 ng/microl of IL-1beta significantly increased the release of PGE2 and NOS activity in the hypothalamus. Treatment with alpha-MSH (0.1 microg/microl) inhibited the effect of IL-1beta on PGE2 release. Also, gamma-MSH (1 microg/microl) eliminated the increase in NOS activity induced by IL-1beta. Our data indicate the modulatory role of melanocortins in the early hypothalamic response to IL-1beta, with different regulation of PGE2 and NO release.