Metabolic and neuroendocrine effects of pro-inflammatory cytokines.
Immune-neuroendocrine interactions occur during physiological and pathological situations. Pro-inflammatory cytokines such as IL-1, IL-6 and TNF alpha play a role in mediating these interactions. Although all three cytokines can stimulate ACTH and glucocorticoid output, IL-1 has the highest potency. It is known that increased glucocorticoid levels result in hyperglycemia. However, administration of low doses of lipopolysaccharide (LPS), an inducer of several cytokines including those mentioned above, causes a profound and long lasting hypoglycaemia. This effect seems to be dissociable from that of insulin, since the same effect was observed in insulin-resistant db/db mice. The data reported here show that IL-1 plays a crucial rôle in the mediation of the hypoglycaemia induced by LPS, since other cytokines released following inoculation of endotoxin, such as TNF alpha and IL-6, have only marginal effects or do not induce hypoglycaemia when administered in doses similar to those of IL-1. The effect of IL-1 seems to be integrated at least in part at CNS level since i.c.v. administration produces hypoglycaemia in spite of the concomitant release of corticosterone. The data reported here reinforce the concept that IL-1 and related cytokines participate in the mediation of immune-neuroendocrine interactions.
Del Rey
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A
Department of Research, University Hospital, Basel, Switzerland.
Besedovsky
H O
HO
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005260:Female; D007249:Inflammation / Q000209:etiology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001786:Blood Glucose; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone