Interleukin-10 reduces morbidity and mortality in murine multiple organ dysfunction syndrome (MODS).

HYPOTHESIS

IL-10 will reduce morbidity and mortality in murine MODS. Introduction. Intraperitoneal (ip) zymosan causes a triphasic inflammatory process leading to MODS. Phase I is an acute systemic inflammatory response to sterile peritonitis. Phase II is the recovery phase. Phase III is characterized by recurrent illness, progressive organ dysfunction, and elevated proinflammatory cytokines.

METHODS

Male ICR mice were randomized (on Experiment Day 0, time = 0 h) into four initial groups (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 received no zymosan and IL-10 at t = 2 h. Group D received zymosan and IL-10 at t = 2 h. On Experiment Day 4, mice in Groups B-D were randomized into six further treatment groups (B1 and B2, C1 and C2, D1 and D2). Group B1 received no treatment. Group B2 received IL-10 when clinical signs of recurrent illness developed (Phase III, 12-18 days after zymosan treatment). Mice were sacrificed when they were preterminal (clinical signs of shaking, shivering, or paralysis) or on Experiment Day 28 (survivors). Plasma total bilirubin and creatinine levels were 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 bilirubin and hemorrhagic lungs which, if left untreated, was lethal. Mice 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 beta1 = 0.082 ml/mm Hg vs 0.059 ml/mm Hg, P < 0.001) compared to untreated (Group B1) mice in Phase III.

CONCLUSIONS

IL-10 improves survival even when given after clinical signs of illness are present.