Cytokine-induced neutrophil chemoattractant 1 (CINC-1) mediates the sympathetic component of inflammatory mechanical hypersensitivitiy in rats

Abstract

The hyperalgesic effect of cytokine-induced neutrophil chemoattractant 1 (CINC-1/CXCL1) was measured in a model of mechanical hyperalgesia in rats. CINC-1 evoked a dose-dependent mechanical hypersensitivity, which was already significant 2 h after the cytokine injection, peaked 4 h after and decreased thereafter. The local pre-treatment of the rats with the beta-adrenoceptor antagonist, atenolol (25 microg paw-1), but not with the cyclooxygenase inhibitor indomethacin (100 microg paw-1), inhibited (86%) the CINC-1-induced hypersensitivity. Conversely, IL-1beta-evoked hypersensitivity was inhibited (76%) by local pre-treatment of the animals with indomethacin, but not by atenolol. Carrageenin- and TNF-alpha-evoked hypersensitivity were attenuated to about the same extent (50%) by antisera neutralising CINC-1 or IL-1beta. The association of both antisera abolished the hypersensitivity effect of carrageenin and TNF-alpha. In addition, carrageenin, LPS and TNF-alpha were shown to stimulate the production of immunoreactive CINC-1 in the skin of injected paws. These data suggest that CINC-1, released at sites of inflammation, mediates inflammatory hyperalgesia in rats via release of sympathomimetic amines.