Cytokine-mediated inflammatory hyperalgesia limited by interleukin-4

1 The effect of IL-4 on responses to intraplantar (i.pl.) carrageenin, bradykinin, TNF alpha, IL-1 beta, IL-8 and PGE(2) was investigated in a model of mechanical hyperalgesia in rats. Also, the cellular source of the IL-4 was investigated. 2 IL-4, 30 min before the stimulus, inhibited responses to carrageenin, bradykinin, and TNF alpha, but not responses to IL-1 beta, IL-8 and PGE(2). 3 IL-4, 2 h before the injection of IL-1 beta, did not affect the response to IL-1 beta, whereas IL-4, 12 or 12+2 h before the IL-1 beta, inhibited the hyperalgesia (-30%, -74%, respectively). 4 In murine peritoneal macrophages, murine IL-4 for 2 h before stimulation with LPS, inhibited (-40%) the production of IL-1 beta but not PGE(2). Murine IL-4 (for 16 h before stimulation with LPS) inhibited LPS-stimulated PGE(2) but not IL-1 beta. 5 Anti-murine IL-4 antibodies potentiated responses to carrageenin, bradykinin and TNF alpha, but not IL-1 beta and IL-8, as well as responses to bradykinin in athymic rats but not in rats depleted of mast cells with compound 40/80. 6 These data suggest that IL-4 released by mast cells limits inflammatory hyperalgesia. During the early phase of the inflammatory response the mode of action of the IL-4 appears to be inhibition of the production TNF alpha, IL-1 beta and IL-8. In the later phase of the response, in addition to inhibiting the production of pro-inflammatory cytokines, IL-4 also may inhibit the release of PGs.