An antipyretic role for interleukin-10 in LPS fever in mice

Am J Physiol. 1999 Jan;276(1):R81-9. doi: 10.1152/ajpregu.1999.276.1.R81.

Abstract

Interleukin (IL)-10 inhibits the synthesis of proinflammatory cytokines implicated in fever, including IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. We hypothesized that IL-10 functions as an antipyretic in the regulation of fevers to lipopolysaccharide (LPS) and turpentine. Body temperature was measured by biotelemetry. Swiss Webster (SW) mice treated with recombinant murine IL-10 were resistant to fever induced by a low dose of LPS (100 microgram/kg ip) and to the hypothermic and febrile effects of a high (septiclike) dose of LPS (2.5 mg/kg ip). IL-10 knockout mice developed an exacerbated and prolonged fever in response to a low dose of LPS (50 microgram/kg ip) compared with their wild-type counterparts. At 4 h after injection of the low dose of LPS, plasma levels of IL-6, but not TNF-alpha, were significantly elevated in the IL-10 knockout mice compared with their wild-type controls (ANOVA, P < 0.05). After injection of the same high dose of LPS injected into SW mice, wild-type mice developed a fever at 24 h whereas IL-10 knockout mice immediately developed a profound hypothermia that lasted through 41 h (ANOVA, P < 0.05). Body weight and food intake were more significantly depressed in response to the high dose of LPS in the knockout mice compared with their wild-type controls. Only 30% of the IL-10 knockout mice survived compared with 100% of the wild-type mice (Fisher's exact test, P < 0.05). Fever in response to the injection of turpentine (100 microliter/mouse sc) did not differ between wild-type and IL-10 knockout mice. These data support the hypotheses that 1) IL-10 functions as an endogenous antipyretic following exposure to LPS, 2) a putative mechanism of the early antipyretic action of IL-10 is through the inhibition of plasma levels of IL-6, 3) IL-10 has a protective role in the lethal effects of exposure to high levels of LPS, and 4) endogenous IL-10 does not have a role in fever induced by turpentine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Body Temperature / drug effects
  • Body Weight / drug effects
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Fever / physiopathology*
  • Interleukin-10 / genetics
  • Interleukin-10 / pharmacology*
  • Interleukin-6 / blood
  • Irritants
  • Lipopolysaccharides* / administration & dosage
  • Lipopolysaccharides* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout / genetics
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha / analysis
  • Turpentine

Substances

  • Analgesics, Non-Narcotic
  • Interleukin-6
  • Irritants
  • Lipopolysaccharides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Turpentine