ObjectiveTo examine the relationship of circulating proinflammatory and anti-inflammatory cytokine concentrations to nitric oxide and organ failure in pediatric sepsis.DesignProspective study.SettingPediatric intensive care unit (ICU), Children's Hospital of Pittsburgh, University of Pittsburgh.PatientsNineteen patients with a diagnosis of sepsis admitted to the pediatric ICU. Twelve uninfected critically ill patients served as controls.InterventionsNone.Measurements and Main ResultsPlasma interleukin (IL)-10, IL-6, and nitrite/nitrate concentrations were measured and compared with an index of organ failure daily for 3 days after presentation with the sepsis syndrome.Children with increased plasma IL-6 concentrations (n equals 6) had increased plasma nitrite/nitrate concentrations (p less than .01 on each day), increased organ failure scores (p less than .05 on days 2 and 3), and the highest plasma IL-10 concentrations (p less than .05 on days 1 and 3, p equals .054 on day 2) when compared with children with sepsis and undetectable IL-6 concentrations. Children with sepsis and detectable IL-6 concentrations, and children with undetectable IL-6 concentrations, both had increased nitrite/nitrate concentrations (p less than .005 on days 1 through 3) and increased IL-10 concentrations (p less than .05 on days 1 and 2) compared with controls. Children with increased IL-6 concentrations had higher organ failure on each day (p less than .01), and children with undetectable IL-6 concentrations had higher organ failure on days 1 and 2 only (p less than .005) when compared with controls. Organ failure improved over time in the children with undetectable IL-6 concentrations (p less than .005).ConclusionsIncreased plasma nitrite/nitrates and increased organ failure scores occurred in the children with sepsis who had an exaggerated proinflammatory state, despite a pronounced anti-inflammatory response. When the anti-inflammatory response predominated, and the proinflammatory state was dampened, organ failure status improved.(Crit Care Med 1996; 24:1137-1143)