title: Role of Th1 and Th2 cytokines in regulating the liver injury induced by delayed-type hypersensitivity to picryl chloride.
abstract: OBJECTIVE
  We have previously reported that a new model of liver injury induced in mice by delayed-type hypersensitivity (DTH) to picryl chloride (PCl) mimicks the pathogenesis of human hepatitis. This liver injury is mediated by CD4+ T cells. The interaction between lymphocyte function associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) is an essential process for hepatocyte (HC) damage. The present study was undertaken to reveal the role of Th1 and Th2-like cytokines in regulating the liver injury.
  
  
  METHODS
  The kinetics of cytokine production were examined by ELISA and RT-PCR after the elicitation of liver injury for both serum protein and liver mRNA expression, respectively. A co-culture assay between liver nonparenchymal cells (NPC) and HC was conducted to evaluate the cytokine regulation on the cell-cell interaction. Expression of LFA-1 on NPC and ICAM-1 on HC were examined by FACScan and ELISA, respectively.
  
  
  RESULTS
  Serum IL-2 and IFN-gamma showed a peak production at 6 and 12 h, while IL-5 and IL-4 reached their maximum levels at 18 and 24 h after induction of liver injury, respectively. Liver mRNA expression of IFN-gamma and IL-4 had a similar time course to their corresponding products. Both recombinant murine IFN-gamma and IL-2 triggered the hepatotoxicity of NPC or spleen cells at 0 h. In this case, an increased expression of both LFA-1 on NPC and ICAM-1 on HC was also observed. In contrast, IL-4 and IL-5 completely abolished the hepatotoxicity of NPC at 12 h without influencing the adhesion molecules.
  
  
  CONCLUSIONS
  Th1 and Th2 may be involved in regulating liver injury. Th1/Th2 balance may critically contribute to the production of the liver injury or recovery from it.
authors.affiliation: Department of Pharmacology for Chinese Materia Medica, China Pharmaceutical University, Nanjing.
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.forename: F
authors.initials: F
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: I
authors.initials: I
authors.lastname: Saiki
authors.forename: A
authors.initials: A
authors.lastname: Koda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D016207:Cytokines / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
chemical_list: D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D010853:Picryl Chloride