A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

• Published in: Memórias do Instituto Oswaldo Cruz 2018-05, Vol.111 (12)
• Main Authors: León-Nava, Marco A de, Álvarez-Delgado, Carolina, Donis-Maturano, Luis, Hernández-Ruiz, Joselin, Manjarrez-Reyna, Aaron N, Cruz-Avilés, Edgar, Leon-Cabrera, Sonia, Morales-Montor, Jorge, Fragoso, José M, Escobedo, Galileo
• Format: Article
• Language: English
• Subjects: acetaminophen; acute liver failure; interleukin; liver disease; parasite infection; Taenia crassiceps
• ISSN: 1678-8060

We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen- induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.