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

¹ From the Department of Pediatrics, University of Pittsburgh School of Medicine
² 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
³ From the Department of Hematology, University of Pittsburgh School of Medicine
⁴ From the Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine

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.

Key Words: children • compensatory anti-inflammatory response syndrome • interleukin 6 • interleukin 10 • multiple organ failure • nitric oxide • sepsis

Submitted on June 17, 1997
Accepted on October 23, 1997

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