The compensatory anti-inflammatory cytokine interleukin 10 response in pediatric sepsis-induced multiple organ failure.
OBJECTIVE
To determine the circulating anti-inflammatory cytokine interleukin 10 (IL-10) response during the development of sepsis-induced multiple organ failure in children.


METHODS
Prospective study.


METHODS
University pediatric ICU.


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


METHODS
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.


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.


CONCLUSIONS
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.
Doughty
L
L
Department of Pediatrics, Wilford Hall Medical Center, Lackland AFB, USA.
Carcillo
J A
JA
Kaplan
S
S
Janosky
J
J
D000293:Adolescent; D001773:Blood Cells / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D007518:Isoantibodies / Q000494:pharmacology; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology; D009500:Neutralization Tests; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology; D018805:Sepsis / Q000150:complications*
D015850:Interleukin-6; D007518:Isoantibodies; D009566:Nitrates; D009573:Nitrites; D011994:Recombinant Proteins; D016753:Interleukin-10