The role of interleukin-6 in the activation of the hypothalamo-pituitary-adrenocortical axis and brain indoleamines by endotoxin and interleukin-1 beta.
Interleukin-6 (IL-6) is one of several cytokines that can stimulate the hypothalamo-pituitary-adrenocortical (HPA) axis. Because IL-6 is produced in response to the administration of endotoxin (LPS) and interleukin-1 (IL-1), it is possible that IL-6 contributes to the neuroendocrine and neurochemical changes induced by them. In this study, intraperitoneal (i.p.) injection of LPS elevated plasma concentrations of IL-6 while activating the HPA axis in a dose-dependent manner. Both responses reached a peak at around 2-3 h. Mouse IL-1beta administration (100 ng, i.p.) induced large increases in plasma corticosterone and a substantial, but short-lived increase in plasma IL-6 with a peak at 2 h. Pretreatment of mice intraperitoneally with a monoclonal antibody to mouse IL-6 significantly attenuated the plasma ACTH and corticosterone responses to LPS at 3 h, but not at 1 h. Anti-IL-6 treatment also attenuated the LPS-induced increases of tryptophan and the serotonin catabolite, 5-hydroxyindoleacetic acid (5-HIAA), but not that of the norepinephrine catabolite, 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG). Pretreatment of mice with anti-IL-6 significantly attenuated the IL-1-induced increases of plasma ACTH and corticosterone at 2 h, but not at 4 h. The IL-1-induced increases of MHPG, tryptophan and 5-HIAA in hypothalamus and brain stem were not significantly altered. These results suggest that IL-6 contributes to the later phases of the LPS- and IL-1-induced stimulations of the HPA axis and to the indoleaminergic responses to LPS, but not to IL-1.
Wang
J
J
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, P.O. Box 33932, Shreveport, LA 71103, USA.
Dunn
A J
AJ
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004731:Endotoxins / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology*; D007211:Indoles / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D010913:Pituitary-Adrenal System / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001679:Biogenic Amines; D004731:Endotoxins; D007211:Indoles; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone