INFLAMMATORY CYTOKINES IN AN EXPERIMENTAL-MODEL FOR THE MULTIPLE ORGAN DYSFUNCTION SYNDROME

Objective: To investigate the alterations in circulating pro-inflammat ory cytokines and cytokine production by peritoneal macrophages during the development of multiple organ dysfunction syndrome, Design: Prosp ective, controlled laboratory study on zymosan-induced generalized inf lammation in mice, Single intraperitoneal administration of zymosan in duces, over a 12-day period, a triphasic illness in mice: the third ph ase, from day 6 onward, resembles multiple organ dysfunction syndrome. Setting: Animal research laboratory, Subjects: C57BL/6CRW mice receiv ed a single intraperitoneal dose of zymosan on day 0, and standard num bers of animals were killed at different time points up until day 12, Measurements and Main Results: Plasma concentrations of interleukin (I L)-1 alpha and IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured from 3 hrs to 12 days after administration of zymosan, A t the same time points, both lipopolysaccharide-stimulated and unstimu lated production of these cytokines by peritoneal macrophages were mea sured in vitro. Plasma TNF and IL-6 concentrations transiently increas ed during the first 24 hrs after administration of zymosan, After 8 da ys, a prominent peak of biologically inactive TNF was observed. Both u nstimulated and lipopolysaccharide-stimulated cytokine production by p eritoneal cells showed profound changes during the experimental period , Conclusions: These findings seem to confirm our hypothesis that the macrophages are in a continuously activated state and altered in their function, when the animals develop multiple organ dysfunction syndrom e, Further studies are needed to elucidate what happens with these cyt okines at the tissue level, to better understand the pathophysiology o f multiple organ dysfunction syndrome.