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.
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.
Butler
L D
LD
Department of Immunology, Pulmonary and Leukotriene Research, Lilly Research Laboratories, Indianapolis, IN 46285.
Layman
N K
NK
Riedl
P E
PE
Cain
R L
RL
Shellhaas
J
J
Evans
G F
GF
Zuckerman
S H
SH
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*
D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003345:Corticosterone