Elevation of serum interleukin 8 levels in acetaminophen overdose in children and adolescents

• Published in: Clinical pharmacology and therapeutics 2001-09, Vol.70 (3), p.280-286
• Main Authors: James, Laura P., Farrar, Henry C., Darville, Toni L., Sullivan, Janice E., Givens, Timothy G., Kearns, Gregory L., Wasserman, Gary S., Simpson, Pippa M., Hinson, Jack A.
• Format: Article
• Language: English
• Subjects: Acetaminophen - poisoning; Acetylcysteine - therapeutic use; Adolescent; Analgesics, Non-Narcotic - poisoning; Chemical and Drug Induced Liver Injury - blood; Child; Child, Preschool; Drug Overdose - blood; Female; Humans; Infant; Interleukin-8 - blood; Liver Function Tests; Male; Prothrombin Time
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1067/mcp.2001.118243

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 α, interleukin 1β, 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 ≥100 IU/L and ≤1000 IU/L. No elevations of tumor necrosis factor α or interleukin 1β 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. Clinical Pharmacology & Therapeutics (2001) 70, 280–286; doi: 10.1067/mcp.2001.118243