Differential dependence of ACTH secretion induced by various cytokines on the integrity of the paraventricular nucleus.
Effect of different cytokines, human recombinant interleukin-1 alpha and beta (IL-1 alpha, IL-1 beta), interleukin-6 and tumor necrosis factor-alpha (TNF) on adrenocorticotropin (ACTH) secretion was compared in sham-operated rats and those with lesions of the hypothalamic paraventricular nucleus. IL-1 alpha was less active than IL-1 beta in stimulating ACTH in sham-operated rats. Intravenous injection of IL-1 beta in sham-operated animals resulted in a rapid elevation of ACTH secretion. Five days after surgical lesion of the paraventricular nucleus, the main hypothalamic source of hypophysiotropic corticotropin-releasing factor-41, the response to IL-1 beta was attenuated but not abolished. This suggests involvement of extra-paraventricular releasing factors in mediation of ACTH-releasing activity of IL-1 beta, altered responsiveness of pituitary to CRFs, and/or direct action of IL-1 beta on the corticotrope cells. TNF resulted in a biphasic stimulation of ACTH concentration, with peaks at 15 min and 90 min. In paraventricular-lesioned, TNF injected rats both of these ACTH peaks disappeared, suggesting that CRFs from the paraventricular origin mediates ACTH-inducing activity of TNF. IL-6 elevated ACTH secretion much later than the other intravenously injected cytokines, the peak was at 1 h in sham-lesioned rats. Paraventricular lesion completely prevented the increase of ACTH plasma levels after IL-6 injection. These data suggest that: (1) Effect of TNF and IL-6 on hypothalamo-pituitary-adrenal axis is mediated through the hypothalamic paraventricular nucleus and (2) IL-1 beta is able to release ACTH even in the absence of hypothalamic drive.
Kovács
K J
KJ
Laboratory of Neuroendocrinology, Institute of Experimental Medicine, Budapest, Hungary.
Elenkov
I J
IJ
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone