Endogenous interleukin-10 is required for the defervescence of fever evoked by local lipopolysaccharide-induced and Staphylococcus aureus-induced inflammation in rats.
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-alpha, IL-1beta, 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.
Cartmell
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National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK. tcartmel@nibsc.ac.uk
Ball
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Bristow
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Mitchell
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Poole
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D000818:Animals; D001831:Body Temperature; D005260:Female; D005334:Fever / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D007249:Inflammation / Q000150:complications* / Q000209:etiology / Q000382:microbiology; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013203:Staphylococcal Infections; D040521:Subcutaneous Tissue / Q000382:microbiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10