Faculty Collaboration Database

Elevation of serum interleukin 8 levels in acetaminophen overdose in children and adolescents. Clin Pharmacol Ther 2001 Sep;70(3):280-6

Date

09/15/2001

Pubmed ID

11557916

DOI

10.1067/mcp.2001.118243

Scopus ID

2-s2.0-0034827022 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

BACKGROUND: Elevations of inflammatory cytokines have been reported in animal models of acetaminophen (INN, paracetamol) toxicity. In addition, interleukin 8, a chemokine, has been found to be elevated in toxin-associated hepatic disease (ie, acute alcoholic hepatitis). The purpose of this study was to measure serum cytokine levels in children and adolescents with acetaminophen overdose and to evaluate relationships between cytokine elevation and hepatotoxicity.

METHODS: Serum levels of tumor necrosis factor alpha, interleukin 1beta, interleukin 6, interleukin 8, and interleukin 10 were measured by ELISA in children and adolescents (n = 35) with acetaminophen overdose. Peak cytokine levels were examined relative to biochemical evidence of hepatocellular injury, nomogram risk assessment, and prothrombin time.

RESULTS: Five patients had aspartate aminotransferase or alanine aminotransferase levels >1000 IU/L, and 4 patients had aspartate aminotransferase or alanine aminotransferase levels > or =100 IU/L and < or =1000 IU/L. No elevations of tumor necrosis factor alpha or interleukin 1beta were detected. Peak interleukin 8, but not interleukin 6 or interleukin 10, correlated with hepatotoxicity (Mann-Whitney exact test, P <.001). The peak interleukin 8 level was greater in patients at high risk by the nomogram combined with those presenting at >15 hours, as compared with other patients (Mann-Whitney U test, P <.01). The interleukin 8 level peaked before aspartate aminotransferase or alanine aminotransferase in 5 of the 9 patients with hepatotoxicity. In addition, interleukin 8 concentrations of >20 pg/mL were associated with peak prothrombin time values (Mann-Whitney exact test, P <.015).

CONCLUSIONS: Interleukin 8 elevation in patients with acetaminophen hepatotoxicity corresponds with other common clinical measures that are predictive of hepatocellular injury. Further study is warranted to evaluate possible mechanistic relationships between inflammatory cytokines and acetaminophen hepatotoxicity in children and adults.

Author List

James LP, Farrar HC, Darville TL, Sullivan JE, Givens TG, Kearns GL, Wasserman GS, Simpson PM, Hinson JA, Pediatric Pharmacology Research Unit Network, National Institute of Child Health and Human Development

Author

Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetaminophen
Acetylcysteine
Adolescent
Analgesics, Non-Narcotic
Chemical and Drug Induced Liver Injury
Child
Child, Preschool
Drug Overdose
Female
Humans
Infant
Interleukin-8
Liver Function Tests
Male
Prothrombin Time