Cytokine‐mediated inflammatory hyperalgesia limited by interleukin‐1 receptor antagonist

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Abstract
The effect of IL‐1ra on response to intraplantar (i.pl.) injection of LPS, carrageenin, bradykinin, TNFα, IL‐1β, IL‐8, PGE2 and dopamine was investigated in a model of mechanical hyperalgesia in rats. IL‐1ra inhibited hyperalgesic response to LPS, carrageenin, bradykinin, TNFα, and IL‐1β, but not responses to IL‐8, PGE2 and dopamine. A sheep anti‐rat IL‐1ra serum potentiated response to LPS, carrageenin, bradykinin, TNFα and IL‐1β but not IL‐8. Carrageenin and LPS stimulated and production of immunoreactive TNFα, IL‐1β and IL‐1ra in the skin of injected paws. The inhibition by IL‐1ra of the hyperalgesic response to carrageenin was not affected by antibodies neutralizing IL‐4 and IL‐10. In mice, IL‐1ra inhibited the nociceptive response to i.p. injection of acetic acid. These data suggest that IL‐1ra, released at sites of inflammation, limits inflammatory hyperalgesia. This effect is independent of (IL‐1ra‐induced) IL‐4 and IL‐10 and appears to be the result of antagonism by IL‐1ra of IL‐1β‐stimulated eicosanoid production. British Journal of Pharmacology (2000) 130, 1418–1424; doi:10.1038/sj.bjp.0703434