IN-VITRO AND IN-VIVO ACTIVITY OF HUMAN INTERLEUKIN-8 IN DOGS

Interleukin-8 (IL-8), a proinflammatory cytokine produced by human mon ocytes, fibroblasts, and endothelial and epithelial cells, is effectiv e not only on cells and tissues of human beings but also on those of s everal animal species. We investigated the importance of recombinant h uman IL-8 for the activation of canine neutrophils in vitro and its po tential for inducing inflammation in vivo. Shape change (10(-9)-10(-7) M IL-8) and chemotaxis (10-(10)-10(-6) M IL-8) assays were used to de termine the activation of canine neutrophils in vitro. Chemotaxis was induced by IL-8 at doses > 10(-8) M with a maximum response at 10(-6) M. A rapid shape change of comparable intensity was elicited by 10(-9) -10(-7) M IL-8. Thirty minutes after intradermal injection of 10(-9) m oles of IL-8, emigration of neutrophils could be observed and became m ore intense at 60 minutes and 240 minutes, respectively. Zymosan-activ ated canine plasma, which served as a positive control, induced a rapi d, massive, and more diffuse neutrophil accumulation, whereas the reac tion after IL-8 was weaker but still significant. The neutrophil accum ulation after IL-8 was preferentially located in perivenular areas of the deep dermis. Recombinant human IL-8 is capable of activating canin e neutrophils in vitro and is able to generate significant neutrophil accumulation in dog skin. Its activity is lower than that in human, ra bbit, and rat systems.