INCREASED BODY-TEMPERATURE, CORTISOL SECRETION, AND HYPOTHALAMIC EXPRESSION OF C-FOS, CORTICOTROPIN-RELEASING HORMONE AND INTERLEUKIN-1-BETA MESSENGER-RNAS, FOLLOWING CENTRAL ADMINISTRATION OF INTERLEUKIN-1-BETA IN THE SHEEP

There is evidence to indicate that cytokines of the interleukin series act within the brain to influence physiological responses to patholog ical states or stressful events. This investigation examined the effec ts of intracerebroventricular (lateral ventricle) injection of human r ecombinant interleukin-1 beta (IL-1 beta) on body temperature, hormone (catecholamine, cortisol, prolactin, growth hormone) release and hypo thalamic expression of c-fos, corticotrophin-releasing hormone (CRH), vasopressin (AVP) and IL-1 beta mRNAs in the sheep. A preliminary stud y showed that central administration of 10 mu g IL-1 beta significantl y (P < 0.05) increased body temperature (by 1.2 degrees C) over a 140 min period but did not affect catecholamine secretion. A second experi ment using graded doses (100 ng, 1 mu g, 10 mu g) of IL-1 beta indicat ed that only the highest dose significantly (P < 0.01) increased corti sol concentrations and that none of the treatments altered the secreti on of prolactin or growth hormone. In a third study, changes in gene e xpression in the hypothalamus were examined using in situ hybridizatio n histochemistry following treatment with 10 mu g IL-1 beta. The resul ts showed that IL-1 beta increased c-fos mRNA in the paraventricular ( PVN, P < 0.05) and supraoptic (SON, P < 0.05) nuclei, CRH mRNA in the PVN (P < 0.01) and IL-1 beta mRNA in the PVN (P < 0.05). There was, ho wever, no change in AVP mRNA in either the PVN or the SON.