Primary role of interleukin-1 alpha and interleukin-1 beta in lipopolysaccharide-induced hypoglycemia in mice

Clin Diagn Lab Immunol. 2002 Nov;9(6):1307-12. doi: 10.1128/cdli.9.6.1307-1312.2002.


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.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Female
  • Glucocorticoids / physiology
  • Hydrocortisone / blood
  • Hypoglycemia / etiology*
  • Insulin / blood
  • Interleukin-1 / physiology*
  • Lipopolysaccharides / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout


  • Blood Glucose
  • Glucocorticoids
  • Insulin
  • Interleukin-1
  • Lipopolysaccharides
  • Hydrocortisone