title: Plasma interleukin-1beta, prolactin, ACTH and corticosterone responses to endotoxin after damage of the anterior hypothalamic area.
abstract: This report concerns the use of an animal model described by us [J Submicrosc Cytol Pathol 1995;27:83-89] to investigate neural and endocrine sites for endotoxin (ENDO, E. coli 055:B5, 200 microg/100 g body weight in saline intravenously) effects on immunomodulatory hormone and cytokine release. Plasma interleukin-1beta (IL-1beta), prolactin (PRL), ACTH and corticosterone responses to ENDO after neurotoxic damage of neurons residing in the anterior hypothalamic area (AHA) were studied in freely behaving male rats. Excitotoxic cell damage in the AHA was produced by bilaterally injecting N-methyl-DL-aspartate (NMA) in artificial cerebrospinal fluid (aCSF) into this brain site. Injections of comparable volumes of aCSF alone served as controls for brain damage associated with the treatment. In both experimental brain manipulations before ENDO challenge the rise in plasma IL-1beta concentrations in response to ENDO was reduced by 2-fold at 1 h and 3- to 5-fold at 3 h when compared to controls. Nevertheless, experimental and control brain manipulations did not modulate the expected rise in corticosterone concentrations after ENDO exposure which rose 5-fold above the baseline level in all animals. However, AHA manipulation did reduce plasma ACTH and prolactin concentrations differentially. Introduction of either NMA or the control injection of aCSF alone into AHA reduced plasma ACTH concentrations by 2-fold at 0.5 and 1 h after ENDO. However, there was a greater reduction in the rise of plasma PRL concentrations after ENDO found in NMA-treated groups versus rats receiving control aCSF. These results demonstrate that variable-size hypothalamic damage (a larger lesion produced in AHA by NMA treatment vs. a smaller lesion control after aCSF) can result in a differential blunting of PRL, IL-1beta and ACTH release into blood in the face of robust, unmodulated corticosterone increases. In summary, these findings revealed a consistent predominant influence of ENDO on adrenal release of corticosterone as a concomitant to differential IL-1beta, ACTH and PRL release after AHA cell loss. In conclusion, these results constitute further evidence for hypothalamic orchestration of a balance between immunotropic and immunosuppressive neuroendocrine-immune events during acute bacterial infection of mammals.
authors.affiliation: Department of Anatomy, University of South Florida, College of Medicine, Tampa, FL 33612-4799, USA. cphelps@hsc.usf.edu
authors.forename: C P
authors.initials: CP
authors.lastname: Phelps
authors.forename: J M
authors.initials: JM
authors.lastname: Dong
authors.forename: L T
authors.initials: LT
authors.lastname: Chen
authors.forename: R A
authors.initials: RA
authors.lastname: Menzies
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000276:immunology*; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood / Q000276:immunology*; D003714:Denervation; D004731:Endotoxins / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood / Q000276:immunology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology*; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011388:Prolactin / Q000097:blood / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000097:blood / Q000139:chemically induced / Q000276:immunology*
chemical_list: D004731:Endotoxins; D018690:Excitatory Amino Acid Agonists; D007375:Interleukin-1; D016202:N-Methylaspartate; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003345:Corticosterone