title: Interleukin-1 receptors in the brain-endocrine-immune axis. Modulation by stress and infection.
abstract: In the present study, we examined the in vitro and in vivo modulation of IL-1 receptors by stress and endotoxin treatment. The treatment of AtT-20 mouse pituitary adenoma cells for 24 h with neuroendocrine mediators of stress such as CRF and catecholamines produced dose-dependent increases in cAMP production and [125I]IL-1 alpha binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF-stimulated cAMP production and decreased both basal and CRF-mediated increases in [125I]IL-1 alpha binding. Furthermore, in keeping with the effects of stress mediators to up-regulate IL-1 receptors in AtT-20 cells, ether-laparotomy stress in mice resulted in a significant increase in [125I]IL-1 alpha binding in the pituitary with no significant alterations observed in the brain; in contrast, [125I]oCRF binding in the pituitary was significantly decreased after the ether-laparotomy stress. Next, we investigated the modulation of IL-1 beta levels and [125I]IL-1 alpha binding following endotoxin treatment. IL-1 beta levels were dramatically increased in the peripheral tissues (pituitary, testis, and spleen) at 2-6 h after a single LPS injection (30 micrograms LPS/mouse); however, no significant changes were observed in brain (hippocampus and hypothalamus). [125I]IL-1 alpha binding in the pituitary gland, liver, spleen, and testis was significantly decreased at 2 h following a single administration of both low (30 micrograms LPS/mouse) and high (300 micrograms LPS/mouse) doses of endotoxin. [125I]IL-1 alpha binding in the hippocampus was not significantly altered at 2 h by low dose of LPS and was significantly decreased by high-dose administration of LPS (300 micrograms/mouse). Following two LPS injections (at 0 and 12 h), dramatic increases in IL-1 beta concentrations in the hypothalamus, hippocampus, spleen, and testis were observed at 2 h after the second LPS injection; a small but statistically nonsignificant change was evident in the pituitary. Moreover, dramatic decreases in [125I]IL-1 alpha binding were seen after two injections of 30 micrograms LPS/mouse in both central and peripheral tissues. These data provide further support for a role for IL-1 in coordinating brain-endocrine-immune responses to stress and infection.
authors.affiliation: Second Department of Internal Medicine, Kochi Medical School, Nankoku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takao
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: E B
authors.initials: EB
authors.lastname: De Souza
mesh_terms: D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004986:Ether / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007813:Laparotomy; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D017472:Receptors, Interleukin-1; D004986:Ether; D005576:Colforsin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D007545:Isoproterenol