Interaction between alcohol and interleukin-1 beta on ACTH secretion and the expression of immediate early genes in the hypothalamus.
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.
Lee
S
S
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Rivier
C
C
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
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