Inhibition by neuropeptides of interleukin-1 beta-induced, prostaglandin-independent hyperalgesia. |
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| Authors: | R. L. Follenfant M. Nakamura-Craig B. Henderson G. A. Higgs |
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| Affiliation: | Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent. |
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| Abstract: | The cytokine interleukin-1 beta (IL-1 beta) is a potent hyperalgesic agent in the rat whereas IL-1 alpha is relatively inactive (Ferreira et al., 1988). IL-1 beta induced a dose-dependent increase in the sensitivity of rat paws to mechanical stimulation following intra-plantar injection but this effect was not reduced by indomethacin (1.0 mg kg-1, p.o.), at a dose known to inhibit completely prostaglandin synthesis in the rat (Salmon et al., 1983). Prostaglandin (PG)E2 enhanced sensitivity to both mechanical pressure and increased temperature but IL-1 beta enhanced only sensitivity to pressure. These observations indicate that IL-1 beta sensitized pressure-sensitive but not temperature-sensitive sensory neurones, through a prostaglandin-independent mechanism. Hyperalgesia induced by IL-1 beta but not PGE2, was inhibited by the neuropeptide melanocyte-stimulating hormone (alpha MSH) and its analogue [Nle4, D-Phe7] alpha MSH which are known to antagonize IL-1 responses in other systems (Holdeman & Lipton, 1985; Cannon et al., 1986). IL-1 beta-induced hyperalgesia was also reduced by the putative IL-1 beta antagonist Lys-D-Pro-Thr (Ferreira et al., 1988) but alpha MSH and its analogue were 10-50 times more potent. |
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