Faculty Collaboration Database

Cytokines and toxicity in acetaminophen overdose. J Clin Pharmacol 2005 Oct;45(10):1165-71

Date

09/21/2005

Pubmed ID

16172181

DOI

10.1177/0091270005280296

Scopus ID

2-s2.0-25444529963 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

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.

Author List

James LP, Simpson PM, Farrar HC, Kearns GL, Wasserman GS, Blumer JL, Reed MD, Sullivan JE, Hinson JA

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
Adolescent
Alanine Transaminase
Aspartate Aminotransferases
Chemokine CCL2
Child
Child, Preschool
Cytokines
Drug Overdose
Enzyme-Linked Immunosorbent Assay
Female
Humans
Infant
Infant, Newborn
Interleukin-10
Interleukin-6
Interleukin-8
Linear Models
Male
Prothrombin Time