Premium
Correlation of MCP1 with toxicity in acetaminophen overdose
Author(s) -
James L. P.,
Simpson P.,
Wasserman G.,
Farrar H. A.,
Kearns G. L.,
Hinson J. A.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.187
Subject(s) - toxicity , medicine , acetaminophen , acute toxicity , gastroenterology , pharmacology
Purpose Studies in animal models of acetaminophen (APAP) toxicity have reported the upregulation of cytokines, some of which are anti‐inflammatory or involved in hepatocyte regeneration. To further study this relationship, cytokines were measured in children/adolescents with acute APAP overdose. Methods: ELISA measurements of IL6, IL8, IL10, and MCP1 were performed on serum samples of APAP overdose patients. Results: 76 patients (age 13.72±4.41 yrs; 64 females) were enrolled and stratified by toxicity subgroups: Grp 1 (no/mild toxicity; AST<100 IU/L, n=51), Grp 2 (moderate toxicity; AST≥100 & ≥1000 IU/L, n=12), Grp 3 (severe toxicity, AST>1000 IU/L, n=13). A significant relationship was present for MCP1 (presented as median, range) (Grp 1, 628.0 pg/mL, 181.6‐1800.4; Grp 2, 1137.3 pg/mL, 167.8‐1808.1; Grp 3, 2777.1 pg/mL, 472.6‐6291.3) and toxicity subgroups (p<0.001). PT was higher (17.6 sec, 11.4‐43.8 vs. 14.1 sec, 10.6‐27.5; p<0.001) in patients with elevated MCP1 and in patients with delays in N‐acetylcysteine (p<0.0003). Grp 2+3 had higher values for IL6 (5.3 pg/mL, 0.0‐58.3, p=0.023) than Grp 1 (0.0 pg/mL, 0.0‐35.2) and higher values for IL8 (17.6 pg/mL, 0.0‐1013.8, p=0.027) than Grp 1 (0.0pg/mL, 0.0–1278.3). Conclusions: MCP1, a cytokine with hepatoprotective properties, appears to have a strong relationship with clinical measures of toxicity/risk in APAP overdose. This study supports the involvement of cytokines in repair processes in APAP toxicity. Clinical Pharmacology & Therapeutics (2004) 75 , P50–P50; doi: 10.1016/j.clpt.2003.11.187