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Interleukin-1β as a potent hyperalgesic agent antagonized by a tripeptide analogue

Abstract

Interleukin-1 (IL-1) describes two inflammatory proteins1, IL-1α and IL-1β, produced by activated macrophages and other cell types2 and encoded by two genes. Their amino acid sequences have only 26% similarity1, but their biological activities are comparable, with a few exceptions3,4; indeed, both molecules appear to act at the same receptor5,6. As IL-1 releases prostaglandins7 which sensitize nociceptors in man and in experimental animals8, we tested IL-1α and IL-1β in rats for hyperalgesic (nociceptive) activity. Our results show that IL-1β given systemically is an extremely potent hyperalgesic agent with a probable peripheral site of action; IL-1α is 3,000 times less active than IL-1β. We have delineated the region of IL-1β mediating the hyperalgesic effect and developed an analgesic tripeptide analogue of IL-1β which antagonizes hyperalgesia evoked by IL-1β and by the inflammatory agent carrageenan.

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Ferreira, S., Lorenzetti, B., Bristow, A. et al. Interleukin-1β as a potent hyperalgesic agent antagonized by a tripeptide analogue. Nature 334, 698–700 (1988). https://doi.org/10.1038/334698a0

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