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