Regulation of macrophage inflammatory protein-1 alpha expression and function by endogenous interleukin-10 in a model of acute inflammation

In this study we have determined the role of endogenous interleukin (IL)-10 on leucocyte recruitment and production of the CC chemokine macrophage inf lammatory protein-1 alpha (MIP-1 alpha) in a murine model of acute inflamma tion. Intraperitoneal injection of zymosan produced a dose-dependent cellul ar infiltration which was concomitant with MIP-1 alpha release in the lavag e fluids. Release of this chemokine had a functional role since treatment o f mice with a specific anti-MIP-1 alpha antibody reduced both neutrophil an d monocyte accumulation into the peritoneal cavity, An unexpected increase in cell influx and MIP-1 alpha production was measured following depletion of resident peritoneal macrophages, as achieved by a 3-day liposome treatme nt. A similar result was obtained when the zymosan peritonitis response was elicited in IL-IO knock-out mice. In summary we propose a functional cross talk between endogenous IL-10 and this CC chemokine during the host inflam matory response. (C) 1999 Academic Press.