Cytokine-mediated inflammatory hyperalgesia limited by interleukin-13

The effect of interleukin-13 (IL-13) on hyperalgesic responses to intraplan tar (i.pl,) injection of carrageenin, E. coli endotoxin (LPS), bradykinin,t umour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), in terleukin-8 (IL-8) and prostaglandin E-2 (PGE(2)) was investigated in a mod el of mechanical hyperalgesia in rats, Also, the cellular source of the IL- 13 was investigated. IL-13, administered 30 min before the stimulus, inhibi ted responses to carrageenin, LPS, bradykinin, and TNF-alpha, but not respo nses to IL-1 beta, IL-8 arid PGE(2), IL-13, administered 2 hours before the injection of IL-1 beta; did not affect the response to IL-1 beta, whereas IL-13, administered 12 hours or 12 + 2 hours before the IL-1 beta,: inhibit ed the hyperalgesia (- 35%, - 77%, respectively). In murine peritoneal macr ophages, IL-13 administered 2 hours before stimulation with LPS, inhibited the production of IL-1 beta (- 67%) and PGE, (- 56%), IL-13 administered 12 hours before stimulation with LPS inhibited LPS-stimulated PGE(2) but not IL-1 beta, An anti-IL-13 serum potentiated responses to carrageenin, LPS, b radykinin and TNF-alpha (but not IL-1 beta and IL-8), as well as responses to bradykinin in rats depleted of mast cells with compound 40/80, but not i n athymic rats. These data suggest that IL-13, released by lymphocytes, lim its inflammatory hyperalgesia by the inhibition of the production TNF-alpha , IL-1 beta, IL-8 and PGs.