Endogenous Interleukin-10 is Required for the Defervescence of Fever Evoked by Local Lipopolysaccharide-Induced and Staphylococcus Aureus-Induced Inflammation in Rats |
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| Authors: | T Cartmell C Ball A F Bristow D Mitchell S Poole |
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| Institution: | National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK;Brain Function Research Unit, School of Physiology, University of the Witwatersrand Medical School, Johannesburg 2193, South Africa |
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| Abstract: | We tested the hypothesis that endogenous interleukin (IL)-10 limits the fever induced by a Gram-negative bacterial toxin ( Escherichia coli lipopolysaccharide, LPS) and a Gram-positive bacterial toxin ( Staphylococcus aureus ), when these toxins are injected into a subcutaneous air pouch ( i.po .) in rats. Injection of LPS or S. aureus caused fevers that were reduced in amplitude and duration by simultaneous administration of rat recombinant IL-10. The inhibition of fever by IL-10 was accompanied by a significant reduction in the toxin-evoked increases in concentrations of immunoreactive IL-6 at the site of inflammation and of IL-6 and IL-1 receptor antagonist in the circulation. Conversely, neutralisation of endogenous IL-10 in the pouch increased the amplitude and dramatically increased the duration of toxin-evoked fever, and augmented toxin-induced increases in pouch tumour necrosis factor-α, IL-1β, and especially IL-6. Our data support a crucial regulatory role for endogenous IL-10 in limiting the fever responses during both Gram-negative and Gram-positive infections. |
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