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

1 The effect of IL-1ra on response to intraplantar (i.pl.) injection of LPS , carrageenin, bradykinin, TNF alpha, IL-1 beta, IL-beta, PGE(2) and dopami ne was investigated in a model of mechanical hyperalgesia in rats. 2 IL-1ra inhibited hyperalgesic response to LPS, carrageenin, bradykinin, T NF alpha, and IL-1 beta, but not responses to IL-8, PGE(2) and dopamine. 3 A sheep anti-rat IL-1ra serum potentiated response to LPS, carrageenin, b radykinin, TNF alpha and IL-1 beta but not IL-8. 4 Carrageenin and LPS stimulated and production of immunoreactive TNF alpha , IL-1 beta and IL-1ra in the skin of injected paws. 5 The inhibition by IL-1ra of the hyperalgesic response to carrageenin was not affected by antibodies neutralizing IL-4 and IL-10. 6 In mice, IL-1ra inhibited the nociceptive response to i.p. injection of a cetic acid. 7 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-1 beta-stimulated eicosanoid production.