IL-1β-mediated innate immunity is amplified in the db/db mouse model of type 2 diabetes

Jason C. O'Connor, Ansuman Satpathy, Matthew E. Hartman, Emily M. Horvath, Keith W. Kelley, Robert Dantzer, Rodney W. Johnson, Gregory G. Freund

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Chronic inflammation appears to play a critical role in type 2 diabetes and its complications. Here we tested the hypothesis that this inflammatory dysregulation affects the IL-1β system and has functional consequences in the brain. Diabetic, db/db, and nondiabetic, db/+, mice were administered i.p. LPS, a potent cytokine inducer, at a dose of 100 μg/kg/mouse. db/db mouse innate immune-associated sickness behavior was 14.8, 33, 44.7, and 34% greater than that of db/+ mice at 2, 4, 8, and 12 h, respectively. When a fixed dose of LPS was used (5 μg/mouse), db/db mouse sickness was again enhanced 18.4, 22.2, and 14.5% at 4, 8, and 12 h as compared with db/+ mice. In diabetic mice, peritoneal macrophages produced more IL-1β in response to LPS, and peritoneal levels of IL-1β induced by LPS were increased. Importantly, IL-1R antagonist and type 2 IL-1 receptor (IL-1R2) failed to up-regulate in response to LPS in db/db mice. Finally, both peripheral and central administration of IL-1β, itself, induced sickness in db/db mice that mimicked the effects of peripheral LPS and was significantly greater than that seen in db/+ mice. Taken together, these results indicate that IL-1β-mediated innate immunity is augmented in db/db mice both at the periphery and in the brain, and the mechanism is due to diabetes-associated loss of IL-1β counterregulation.

Original languageEnglish (US)
Pages (from-to)4991-4997
Number of pages7
JournalJournal of Immunology
Volume174
Issue number8
StatePublished - Apr 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    O'Connor, J. C., Satpathy, A., Hartman, M. E., Horvath, E. M., Kelley, K. W., Dantzer, R., Johnson, R. W., & Freund, G. G. (2005). IL-1β-mediated innate immunity is amplified in the db/db mouse model of type 2 diabetes. Journal of Immunology, 174(8), 4991-4997.