Cytokines and toxicity in acetaminophen overdose.
Several cytokines have been reported to have hepatoprotective properties in animal models of acetaminophen toxicity. To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood samples were collected from patients following acute ingestions of acetaminophen. Samples for cytokine analysis were collected at the time of routine clinical monitoring in 111 patients (90 females; mean age 13.6 years). Plasma concentrations of interleukin 6, interleukin 8, interleukin 10, and monocyte chemoattractant protein 1 were analyzed by enzyme-linked immunosorbent assay. Patients were stratified by toxicity severity, defined by the maximal values of hepatic transaminase elevation. Levels of interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 were higher in patients with serum alanine aminotransferase > 1000 IU/L, and monocyte chemoattractant protein 1 had the strongest association with toxicity. Monocyte chemoattractant protein 1 values were higher in patients with greater delays in N-acetylcysteine treatment and in patients with higher values of prothrombin time. Monocyte chemoattractant protein 1 elevation in acetaminophen overdose may represent an innate, immunomodulary response of the liver to earlier events in the toxicity. An understanding of the role of cytokine responses in acetaminophen overdose may be relevant to the future development of new therapies for acetaminophen toxicity.
James
Laura P
LP
Department of Pediatrics, Section of Clinical Pharmacology and Toxicology, Arkansas Children's Hospital, 800 Marshall Street, Little Rock, AR 72202, USA. Jameslaurap@uams.edu
Simpson
Pippa M
PM
Farrar
Henry C
HC
Kearns
Gregory L
GL
Wasserman
Gary S
GS
Blumer
Jeffrey L
JL
Reed
Michael D
MD
Sullivan
Janice E
JE
Hinson
Jack A
JA
D000082:Acetaminophen / Q000506:poisoning*; D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D062787:Drug Overdose; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D016014:Linear Models; D008297:Male; D011517:Prothrombin Time
D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D016753:Interleukin-10; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase