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The Compensatory Anti-inflammatory Cytokine Interleukin 10 Response in Pediatric Sepsis-Induced Multiple Organ Failure

Lesley Doughty; Joseph A. Carcillo; Sandra Kaplan; Janine Janosky
Author and Funding Information

Affiliations: From the Department of Pediatrics, University of Pittsburgh School of Medicine,  From the Department of Wilford Hall Medical Center, Lackland AFR, and the Department of Anesthesiology and Critical Care Medicine, Pediatrics, Center for Clinical Pharmacology, University of Pittsburgh School of Medicine,  From the Department of Hematology, University of Pittsburgh School of Medicine,  From the Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine

Affiliations: From the Department of Pediatrics, University of Pittsburgh School of Medicine,  From the Department of Wilford Hall Medical Center, Lackland AFR, and the Department of Anesthesiology and Critical Care Medicine, Pediatrics, Center for Clinical Pharmacology, University of Pittsburgh School of Medicine,  From the Department of Hematology, University of Pittsburgh School of Medicine,  From the Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine

Affiliations: From the Department of Pediatrics, University of Pittsburgh School of Medicine,  From the Department of Wilford Hall Medical Center, Lackland AFR, and the Department of Anesthesiology and Critical Care Medicine, Pediatrics, Center for Clinical Pharmacology, University of Pittsburgh School of Medicine,  From the Department of Hematology, University of Pittsburgh School of Medicine,  From the Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine

Affiliations: From the Department of Pediatrics, University of Pittsburgh School of Medicine,  From the Department of Wilford Hall Medical Center, Lackland AFR, and the Department of Anesthesiology and Critical Care Medicine, Pediatrics, Center for Clinical Pharmacology, University of Pittsburgh School of Medicine,  From the Department of Hematology, University of Pittsburgh School of Medicine,  From the Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine


1998 by the American College of Chest Physicians


Chest. 1998;113(6):1625-1631. doi:10.1378/chest.113.6.1625
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Published online

Abstract

Study objectives: To determine the circulating anti-inflammatory cytokine interleukin 10 (IL-10) response during the development of sepsis-induced multiple organ failure in children.

Design: Prospective study.

Setting: University pediatric ICU.

Patients: Fifty-three consecutive children with sepsis and 15 critically ill children without sepsis.

Interventions: Plasma IL-10, interleukin 6 (IL-6), and nitrite+nitrate (stable end products of nitric oxide) levels and an organ failure index (OFI indicating the number of failing organ systems) were determined in 53 children on days 1 to 3 of sepsis and in control children on day 1. The effect of exogenous human IL-10 or neutralizing IL-10 antibody on supernatant IL-6 levels in ex vivo whole blood culture from 17 children on day 1 of sepsis.

Measurements and results: Children with three or more organ failures had higher plasma IL-10 levels than children with less than 3 organ failures (days 1 and 3; p<0.05). Children who developed sequential pulmonary/hepatic/renal failure had higher IL-10 levels (days 1 to 3; p<0.05). Nonsurvivors had higher IL-10 levels (day 3; p<0.05). IL-10 levels correlated with IL-6 levels (days 1 and 2) and nitrite+nitrate levels (days 1 and 3; p<0.05). Whole blood samples incubated ex vivo with exogenous recombinant human IL-10 had decreased supernatant IL-6 levels (p<0.05) and neutralizing IL-10 antibody showed no significant effect.

Conclusion: A persistent compensatory anti-inflammatory cytokine response characterizes sepsis-induced multiple organ failure. Administration of exogenous IL-10 may inhibit the early proinflammatory response; however, identification of individual immune responsiveness and possibility of persistent infection could be important to rational use in the later stages of pediatric sepsis.


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