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Published on: May 2, 2017
Interleukin-10 reduces morbidity and mortality in murine multiple organ dysfunction syndrome (MODS)
T J Ferrer1, J W Webb, B H Wallace
1Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
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.
Insights
Interleukin-10 (IL-10) treatment significantly reduced mortality and improved survival in mice with multiple organ dysfunction syndrome (MODS). This cytokine therapy demonstrated efficacy even when administered after the onset of severe illness symptoms.
Area of Science:
- Immunology
- Pathophysiology
- Pharmacology
Background:
- Zymosan-induced peritonitis in mice triggers a triphasic inflammatory response, leading to multiple organ dysfunction syndrome (MODS).
- Phase III of this process is characterized by recurrent illness, progressive organ dysfunction, and elevated pro-inflammatory cytokines, often proving lethal.
- Interleukin-10 (IL-10) is investigated for its potential to mitigate the severity of MODS.
Purpose of the Study:
- To evaluate the therapeutic effect of Interleukin-10 (IL-10) on reducing morbidity and mortality in a murine model of multiple organ dysfunction syndrome (MODS).
- To determine if IL-10 administration can improve organ function and survival rates during the critical Phase III of zymosan-induced MODS.
Main Methods:
- Male ICR mice were subjected to zymosan-induced peritonitis and randomized into control and treatment groups.
- One group received IL-10 treatment only after the onset of Phase III clinical signs of recurrent illness.
- Organ function was assessed by plasma bilirubin and creatinine levels, and pulmonary compliance was measured terminally.
Main Results:
- Untreated mice entering Phase III consistently progressed to lethal MODS, characterized by elevated bilirubin and lung hemorrhage.
- Mice treated with IL-10 during Phase III exhibited significantly lower mortality (28.6% vs. 100%) and longer survival (25 vs. 18 days).
- IL-10 treatment also led to improved lung pulmonary compliance compared to untreated controls.
Conclusions:
- Interleukin-10 (IL-10) demonstrates significant therapeutic potential in improving survival and mitigating organ dysfunction in a murine model of MODS.
- IL-10 is effective even when administered therapeutically after the manifestation of clinical signs of severe illness.
- These findings suggest IL-10 as a viable treatment strategy for managing critical illness and MODS.
