title: Interaction between alcohol and interleukin-1 beta on ACTH secretion and the expression of immediate early genes in the hypothalamus.
abstract: We have observed that alcohol does not alter adrenocorticotropin (ACTH) released in response to the iv injection of interleukin-1 beta (IL-1 beta). In contrast, prior (-30 to -90 min) administration of moderate doses of alcohol (0.5-2.0 g/kg) significantly blunts ACTH secretion following the intracerebroventricular (icv) injection of the cytokine. We explored two possible mechanisms responsible for this phenomenon: Corticosteroid feedback and alcohol-induced inhibition of hypothalamic neuronal activation (measured through changes in c-fos and NGFI-B mRNA levels). Increasing plasma corticosterone levels by exposing rats to mild electroshocks or injecting them with corticosterone did not alter ACTH released by rats administered with IL-1 beta into the brain ventricles. Alcohol, which by itself did not stimulate c-fos or NGFI-B mRNA levels in the paraventricular nucleus of the hypothalamus, significantly blunted the ability of icv IL-1 beta to increase the expression of these immediate early genes. We conclude that the inhibitory influence exerted by prior alcohol treatment on ACTH released by icv administered IL-1 beta may reflect an interference with the stimulatory influence of the cytokine on hypothalamic neurons involved in the activation of the hypothalamic-pituitary-adrenal axis.
authors: Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
authors: S
authors: S
authors: Lee
authors: C
authors: C
authors: Rivier
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D007375:Interleukin-1; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone