CRF-DEPENDENT AND CRF-INDEPENDENT MECHANISMS INVOLVED IN HYPOPHYSEAL-ADRENAL SYSTEM ACTIVATION BY BACTERIAL-ENDOTOXIN

The immune system and the hypothalamic-pituitary-adrenal (HPA) axis pl ay important role in the overall inflammatory response. The mechanism through which lipopolysaccharide (LPS, endotoxin) stimulates the HPA a xis is not well understood. In order to clarify the role of hypophysio tropic peptides of paraventricular origin in the effect of LPS on ACTH and corticosterone secretion, the effect of LPS was studied on rats w ith lesions of hypothalamic paraventricular nucleus (PVN). It was show n that 90 min after 2 mg/kg LPS i.p. the ACTH, but not the corticoster one response was effectively blunted in PVN-lesioned rats, as compared to sham operated animals. However, in PVN-lesioned rats 240 min after treatment with LPS a significantly higher plasma ACTH and corticoster one level was monitored. It is, therefore, suggested that in response to LPS activation of HPA both CRF(s)-dependent and CRF(s)-independent mechanisms are involved, even a direct effect of the adrenal cortex sh ould be taken into account.