sFas and sFas ligand and pediatric sepsis-induced multiple organ failure syndrome.
The Fas-Fas ligand system is important for apoptosis of activated immune cells. Perturbation of this system occurs in diseases with dysregulated inflammation. Increased soluble Fas (sFas) occurs in systemic inflammatory response syndrome (SIRS) and can block apoptosis. Increased shedding of FasL (sFasL) occurs in viral infection and hepatitis. Although dysregulated inflammation is associated with sepsis-induced multiple organ failure (MOF) in children, a role for Fas has not been established. We hypothesize that 1) sFas will be increased in children with severe and persistent sepsis-induced MOF and will correlate with inflammatory markers suggesting a role for sFas in inflammatory dysregulation in severe sepsis, and 2) sFasL will be increased when viral sepsis or sepsis-induced liver failure-associated MOF is present in children. Plasma sFas, sFasL, IL-6, IL-10, nitrite + nitrates, and organ failure scores were measured on d 1 and d 3 in 92 children with severe sepsis and 12 critically ill control children. sFas levels were increased in severe sepsis, continued to increase in persistent MOF and nonsurvivors, and were correlated with serum inflammatory markers (IL-6, IL-10, nitrite + nitrate levels). In contrast, sFasL was not increased in severe sepsis and did not correlate with inflammation. sFasL was, however, increased in liver failure-associated MOF and in nonsurvivors, and was associated with viral infection. At autopsy, hepatocyte destruction and lymphocyte infiltration were associated with increased sFas and sFasL levels. sFas may interfere with activated immune cell death and contribute to dysregulation of inflammation, worsening outcome from severe sepsis. sFasL may contribute to hepatic injury and the development of liver failure-associated MOF.
Doughty
Lesley
L
Department of Pediatrics, Rhode Island Hospital, Providence, Rhode Island 02903, USA.
Clark
Robert S B
RS
Kaplan
Sandra S
SS
Sasser
Howell
H
Carcillo
Joseph
J
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000097:blood*; D018448:Models, Immunological; D009102:Multiple Organ Failure / Q000209:etiology* / Q000276:immunology* / Q000503:physiopathology; D018805:Sepsis / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D012995:Solubility; D019014:fas Receptor / Q000097:blood*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D019014:fas Receptor