INTERLEUKIN-10 REDUCES MORBIDITY AND MORTALITY IN MURINE MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS)

Hypothesis. IL-10 mill reduce morbidity and mortality in murine MODS. Introduction. Intraperitoneal (ip) zymosan causes a triphasic inflamma tory process leading to MODS. Phase I is an acute systemic inflammator y response to sterile peritonitis. Phase II is the recovery phase. Pha se III is characterized by recurrent illness, progressive organ dysfun ction, and elevated proinflammatory cytokines. Methods. Male ICR mice were randomized (on Experiment Day 0, time = 0 h) into four initial gr oups (A-D): Control Group A received no zymosan and no IL-10, Group B received zymosan (1 mg/g mouse BW, t = 0) and no IL-10. Group C receiv ed no zymosan and IL-IO at t = 2 h. Group D received zymosan and IL-IO at t = 2 h. On Experiment Day 4, mice in Groups B-D were randomized i nto six further treatment groups (B1 and B2, C1 and C2, D1 and D2). Gr oup B1 received no treatment. Group B2 received IL-10 when clinical si gns of recurrent illness developed (Phase III, 12-18 days after zymosa n treatment). Mice were sacrificed when they were preterminal (clinica l signs of shaking, shivering, or paralysis) or on Experiment Day 28 ( survivors). Plasma total bilirubin and creatinine levels mere measures of organ function. Terminal pulmonary compliance was measured in situ through a physiologic range of tidal volumes. Results. Mice entering Phase III consistently progressed to MODS characterized by elevated bi lirubin and hemorrhagic lungs which, if left untreated, was lethal. Mi ce treated with IL-10 (Group B2) when they entered Phase III had lower mortality (28.6% vs 100%, P < 0.02), longer survival (25 vs 18 days, P < 0.05), and improved lung pulmonary compliance (slope beta(1) = 0.0 82 ml/mm Hg vs 0.059 ml/mm Hg, P < 0.001) compared to untreated (Group B1) mice in Phase III. Conclusions. IL-IO improves survival even when given after clinical signs of illness are present. (C) 1998 Academic Press.