Primary role of interleukin-1 alpha and interleukin-1 beta in lipopolysaccharide-induced hypoglycemia in mice.
Within a few hours of its injection into mice, lipopolysaccharide (LPS) induces hypoglycemia and the production of various cytokines. We previously found that interleukin-1 alpha (IL-1 alpha), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) induce hypoglycemia and that the minimum effective dose of IL-1 alpha or IL-1 beta is about 1/1000 that of TNF-alpha. In the present study, we examined the contribution made by IL-1 to the hypoglycemic action of LPS. Nine other cytokines tested were all inactive at inducing hypoglycemia. LPS produced hypoglycemia in mice deficient in either IL-1 alpha or IL-1 beta but not in mice deficient in both cytokines (IL-1 alpha and -1 beta knockout [IL-1 alpha/beta KO] mice). IL-1 alpha, IL-1 beta, and TNF-alpha induced hypoglycemia in IL-1 alpha/beta KO mice, as they did in normal control mice. The LPS-induced elevation of serum cortisol was weaker in IL-1 alpha/beta KO mice than in control mice, and, in the latter, serum cortisol was markedly raised while blood glucose was declining. IL-1 alpha decreased blood glucose both in NOD mice (which have impaired insulin production) and in KK-Ay mice (insulin resistant). These results suggest that (i). cortisol may not be involved in mediating the resistance of IL-1 alpha/beta KO mice to the hypoglycemic action of LPS, (ii). as a mediator, IL-1 is a prerequisite for the hypoglycemic action of LPS, (iii). IL-1 alpha and IL-1 beta perform mutual compensation, and (iv). IL-1 plays a role as the primary stimulator of the many anabolic reactions required for the elaboration of immune responses against infection.
Oguri
Senri
S
Departments of Pharmacology. Maxillofacial and Plastic Surgery, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-Machi, Aoba-Ku, Sendai 980-8575, Japan.
Motegi
Katsutoshi
K
Iwakura
Yoichiro
Y
Endo
Yasuo
Y
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005938:Glucocorticoids / Q000502:physiology; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000209:etiology*; D007328:Insulin / Q000097:blood; D007375:Interleukin-1 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D007375:Interleukin-1; D008070:Lipopolysaccharides; D006854:Hydrocortisone