The compensatory anti-inflammatory cytokine interleukin 10 response in pediatric sepsis-induced multiple organ failure.

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.