LIPOPOLYSACCHARIDE MODULATION OF EICOSANOID AND CORTICOTROPIN-RELEASING HORMONE-RELEASE FROM RAT HYPOTHALAMIC EXPLANTS AND ASTROCYTE CULTURES IN-VITRO - EVIDENCE FOR THE INVOLVEMENT OF PROSTAGLANDIN E(2) BUT NOT PROSTAGLANDIN-F2-ALPHA AND LACK OF EFFECT OF NERVE GROWTH-FACTOR

Bacterial Lipopolysaccharide (LPS) and prostaglandins (PG) E(2) and F-2 alpha, are putative activators of the hypothalamo-pituitary-adrenal axis. Certain of the biological effects of LPS may be mediated by cytokines such as interleukin-1 beta (IL-1 beta), while IL-1 beta itself may operate via induction of the prostaglandins and/or nerve growth factor (NGF). As IL-1 beta stimulates the release of corticotrophin-releasing hormone (CRH) from acute rat hypothalamic explants directly, the effects of these substances on the release of CRH in vitro were investigated in short- and medium-term (20 and 60 min) incubations. The effect of LPS on the release of PGE(2) and PGF(2 alpha) from these explants, as well as from cortical astrocyte cultures, was also studied. LPS did not modify the release of CRH, PGE(2) or PGF(2 alpha) in 20-min incubations. In 60-min incubations, LPS stimulated the release of PGE(2), whereas the release of CRH was weakly, but significantly, reduced; PGF(2), was not altered. PGE(2) significantly stimulated CRH release in the 60-min but not in the 20-min experiments. This effect appeared to be selective for PGE(2), since PGF(2 alpha), did not modify CRH release, alone or in combination. LPS also selectively released PGE(2) but not PGF(2 alpha) from cortical astrocyte cultures after 24-h incubation. NGF had no effect on the release of explant CRH, regardless of the length of incubation. It was concluded that neither LPS nor NGF acutely stimulate the hypothalamo-pituitary-adrenal axis by a direct action on hypothalamic CRH, while hypothalamic PGE(2) may mediate, at least in part, certain of the neuroendocrine responses to LPS.