Interleukin 10 mitigates the development of the zymosan-induced multiple organ dysfunction syndrome in mice

We investigated the effect of interleukin 10 on the development of zymosan- induced multiple organ dysfunction syndrome (MODS) and on plasma concentrat ions and production capacity of tumour necrosis factor (TNF)-alpha by perit oneal cells. Groups of C57BL/6 mice received a single intraperitoneal injec tion with zymosan, a cell wall component of Saccharomyces cerevisiae, at da y 0, Daily doses of human recombinant interleukin 10 (IL-10: 10 or 50 mu g/ kg) were given intraperitoneally either starting directly before administra tion of zymosan (day 0), or 5 or 8 days after administration of zymosan, Th e animals were monitored for survival, condition, body weight and temperatu re. On day 12 all surviving animals were killed to obtain plasma, organs an d peritoneal cells. Plasma concentrations of TNF-alpha and lipopolysacchari de-stimulated production of TNF-alpha by peritoneal cells were measured; or gan weights were registered as an indicator for organ damage. IL-10 improve s survival and clinical condition and also reduces organ damage, but only a t the highest dose used and only when started simultaneously with the admin istration of zymosan. Circulating TNF-alpha concentrations 12 days after zy mosan are not affected by any of the IL-10 schedules used. However, lipopol ysaccharide-stimulated production of TNF-alpha by peritoneal cells is incre ased, in a dose- and time-dependent fashion. The anti-inflammatory cytokine IL-10 is able to attenuate the development of MODS in this model, but only when given simultaneously with zymosan, and in high dosages, (C) 1999 Acad emic Press.