title: Neuroendocrine regulation of in vivo cytokine production and effects: I. In vivo regulatory networks involving the neuroendocrine system, interleukin-1 and tumor necrosis factor-alpha.
abstract: We have investigated the in vivo regulatory network involving the neuroendocrine system, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF). Adrenalectomy or hypophysectomy shifted the sensitivity curve to lipopolysaccharide (LPS)-induced lethal shock as well as TNF- and IL-1-induced deaths. Serum levels of IL-1 or TNF were altered in adrenalectomized or hypophysectomized mice following in vivo stimulation with LPS when compared to appropriate sham-operated control mice. Exogenous administration of either IL-1 or TNF could induce increases in serum corticosterone in sham-operated mice. Finally, treatment of adrenalectomized mice with corticosterone or dexamethasone could inhibit the induction of serum IL-1 and TNF and modified the pattern of these cytokine-induced deaths. Dexamethasone was more effective in these conditions than the natural glucocorticoid, corticosterone. Taken together, these data provide in vivo evidence for a feedback system involving the neuroendocrine axis (hypothalamus, pituitary and adrenal glands) leading to corticosterone production and subsequent regulation and/or modulation of IL-1 or TNF levels or activity.
authors.affiliation: Department of Immunology, Pulmonary and Leukotriene Research, Lilly Research Laboratories, Indianapolis, IN 46285.
authors.forename: L D
authors.initials: LD
authors.lastname: Butler
authors.forename: N K
authors.initials: NK
authors.lastname: Layman
authors.forename: P E
authors.initials: PE
authors.lastname: Riedl
authors.forename: R L
authors.initials: RL
authors.lastname: Cain
authors.forename: J
authors.initials: J
authors.lastname: Shellhaas
authors.forename: G F
authors.initials: GF
authors.lastname: Evans
authors.forename: S H
authors.initials: SH
authors.lastname: Zuckerman
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D001685:Biological Factors / Q000096:biosynthesis* / Q000097:blood; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D016207:Cytokines; D003907:Dexamethasone / Q000494:pharmacology; D007016:Hypophysectomy; D007375:Interleukin-1 / Q000008:administration & dosage / Q000097:blood*; D051379:Mice; D009490:Neurosecretory Systems / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000032:analysis*
chemical_list: D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003345:Corticosterone