Interleukin-4 deficiency protects mice from acetaminophen-induced liver injury and inflammation by prevention of glutathione depletion

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• 作者：Daniele Araújo Pires (1)
  Pedro Elias Marques (1)
  Rafaela Vaz Pereira (1)
  Bruna Araújo David (1)
  Lindisley Ferreira Gomides (1)
  Ana Carolina Fialho Dias (2)
  Albená Nunes-Silva (3)
  Vanessa Pinho (3)
  Denise Carmona Cara (1)
  Leda Quercia Vieira (2)
  Mauro Martins Teixeira (2)
  Gustavo Batista Menezes (1)
  
• 关键词：Interleukin ; 4 ; Liver injury ; Acetaminophen ; Glutathione
• 刊名：Inflammation Research
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：63
• 期：1
• 页码：61-69
• 全文大小：774 KB
• 作者单位：Daniele Araújo Pires (1)
  Pedro Elias Marques (1)
  Rafaela Vaz Pereira (1)
  Bruna Araújo David (1)
  Lindisley Ferreira Gomides (1)
  Ana Carolina Fialho Dias (2)
  Albená Nunes-Silva (3)
  Vanessa Pinho (3)
  Denise Carmona Cara (1)
  Leda Quercia Vieira (2)
  Mauro Martins Teixeira (2)
  Gustavo Batista Menezes (1)
  
  1. Laboratório de Imunobiofot?nica, Departamento de Morfologia, ICB, Universidade Federal de Minas Gerais, Av. Antonio Carlos, Pampulha, Belo Horizonte, MG, 6627, Brazil
  2. Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
  3. Laboratório de Resolu??o da Resposta Inflamatória, Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
  
• ISSN：1420-908X

文摘

Objective Interleukin-4 (IL-4) is a multifunctional cytokine involved in many diseases such as autoimmune hepatitis and idiosyncratic drug reactions. However, its role in acetaminophen (APAP)-induced liver injury remains unclear. Our objective was to evaluate the contribution of IL-4 to the pathogenesis of APAP-induced liver injury. Methods Balb/C (WT) and IL-4 knockout (IL-4??/sup>) mice were orally overdosed with APAP. After 24?h, survival percentage, biochemical and morphological markers of liver injury, and tissue inflammation were assessed. Results IL-4??/sup> mice were protected from APAP toxicity. Intravital confocal microscopy, tissue histology and serum ALT levels showed significantly less liver injury and inflammation than in the WT group, which may explain the increased survival rate of IL-4??/sup> mice. In addition, IL-4??/sup> mice had decreased production of tumor necrosis factor α, CXCL1 and interleukin-1β in the liver, but not in a remote site such as the lungs. Hepatic macrophage activation was markedly reduced in IL-4-deficient mice. In addition, glutathione depletion—a primary cause of APAP-mediated injury—was significantly attenuated in IL-4??/sup> mice. Conclusions Taken together, our data demonstrate that IL-4??/sup> mice are protected from APAP-induced liver injury due to reduced depletion of glutathione, which prevented liver damage and tissue inflammation.