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

Inflammatory stress due to infection by various microorganisms is known to activate the hypothalamo-pituitary-adrenocortical (HPA) axis through inflam matory mediators. Recently, pituitary-adenylate-cyclase-activating polypept ide (PACAP) was shown to be located in corticotropin-releasing factor conta ining neurons of the medial parvocellular part of the hypothalamic paravent ricular nucleus (mpPVN). In the present study, we demonstrate that PACAP ge ne expression is induced in neurons of the mpPVN after intraperitoneal admi nistration of bacterial lipopolysaccharide (LPS) which was accompanied by a marked increase in PACAP immunoreactivity in the external zone of the medi an eminence. As determined by quantitative in situ hybridization, PACAP gen e expression was rapidly induced after 4 h and was elevated for 48 h, decli ning to normal levels after 72 h. A significant increase in PACAP mRNA was also observed following intraperitoneal injection of interleukin-1 beta. PA CAP gene expression was not induced by LPS in vagotomized animals, suggesti ng that the increase in PACAP mRNA following immune activation by LPS is me diated via the vagus nerve. The findings suggest that PACAP may function as a hypothalamo-pituitary-releasing factor during acute inflammation.