Acute intrahippocampal injection of human interleukin-1 beta stimulates the anterior pituitary POMC transcription and increases plasma levels of ACTHand corticosterone in the male rat

It has been well documented that interleukin-1 beta (IL-1 beta) is a major mediator for recruiting the hypothalamo-pituitary-adrenal (HPA) axis follow ing infectious disease. The recent localization of IL-1 beta receptors in n eurons of the hippocampus provides further support for the role of IL-1 bet a as a neurotransmitter/neuromodulator in the central nervous system. In th is study, we investigated whether an acute intrahippocampal injection of IL -1 beta is able to rapidly stimulate HPA activity. Seven days after bilater al implantation of a guide cannula into the hippocampus, human IL-1 beta (1 0 ng/0.5 mu l/side) was injected to freely moving male rats. Following this , animals were sacrificed at times 20, 45 and 90 min postinjection and a ki netic analysis of hIL-1 beta action on plasma ACTH and corticosterone (CORT ) concentrations and nuclear processing of the anterior pituitary (AP) proo piomelanocortin (POMC) was conducted. Intrahippocampal administration of hI L-1 beta significantly increased both plasma ACTH and CORT concentrations a t 45 and 90 min postinjection. This increase in ACTH concentration parallel ed a rise in AP POMC gene transcription. Moreover, the increase in AP POMC primary transcript was followed by an increase in AP POMC intermediate proc essing RNA. However, at these times, no significant hIL-1 beta effect on th e level of AP nuclear POMC mRNA was observed. Almost identical results were obtained after intraperitoneal injection of hIL-1 beta. In conclusion, our data demonstrates that the hippocampal IL-1 beta/IL-1 beta receptor is dir ectly and rapidly implicated in HPA activation, in the same manner as that observed after intraperitoneal administration of hIL-1 beta. These results show that IL-1 action in the hippocampus could be of immunoneuroendocrine s ignificance for the HPA axis activation during inflammatory states.