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Am J Physiol Regul Integr Comp Physiol 276: R81-R89, 1999;
0363-6119/99 $5.00
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Vol. 276, Issue 1, R81-R89, January 1999

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

Lisa R. Leon, Wieslaw Kozak, Karin Rudolph, and Matthew J. Kluger

Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185

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 µg/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 µg/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 µl/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.

acute phase response; anorexia; hypothermia; temperature regulation; sepsis; lipopolysaccharide


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