PACAP gene expression in neurons of the rat hypothalamo-pituitary-adrenocortical axis is induced by endotoxin and interleukin-1β

Inflammatory stress due to infection by various microorganisms is known to activate the hypothalamo-pituitary-adrenocortical (HPA) axis through inflammatory mediators. Recently, pituitary-adenylate-cyclase-activating polypeptide (PACAP) was shown to be located in corticotropin-releasing factor containing neurons of the medial parvocellular part of the hypothalamic paraventricular nucleus (mpPVN). In the present study, we demonstrate that PACAP gene expression is induced in neurons of the mpPVN after intraperitoneal administration of bacterial lipopolysaccharide (LPS) which was accompanied by a marked increase in PACAP immunoreactivity in the external zone of the median eminence. As determined by quantitative in situ hybridization, PACAP gene expression was rapidly induced after 4 h and was elevated for 48 h, declining to normal levels after 72 h. A significant increase in PACAP mRNA was also observed following intraperitoneal injection of interleukin-1 beta. PACAP gene expression was not induced by LPS in vagotomized animals, suggesting that the increase in PACAP mRNA following immune activation by LPS is mediated via the vagus nerve. The findings suggest that PACAP may function as a hypothalamo-pituitary-releasing factor during acute inflammation.