Role of Th1 and Th2 cytokines in regulating the liver injury induced by delayed-type hypersensitivity to picryl chloride

Aims/Background: We have previously reported that a new model of liver inju ry induced in mice by delayed-type hypersensitivity (DTH) to picryl chlorid e (PCI) mimicks the pathogenesis of human hepatitis. This liver injury is m ediated by CD4(+) T cells. The interaction between lymphocyte function asso ciated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) is an essential process for hepatocyte (HC) damage. The present study was unde rtaken to reveal the role of Th1 and Th2-like cytokines in regulating the l iver injury. Methods. The kinetics of cytokine production were examined by ELISA and RT-PCR after the elicitation of liver injury for both serum prote in and liver mRNA expression, respectively. A co-culture assay between live r nonparenchymal cells (NPC) and HC was conducted to evaluate the cytokine regulation on the cell-cell interaction. Expression of LFA-1 on NPC and ICA M-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 I L-4 reached their maximum levels at Is and 24 h after induction of liver in jury, respectively. Liver mRNA expression of IFN-gamma and IL-4 had a simil ar 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 H C was also observed. In contrast, IL-4 and IL-5 completely abolished the he patotoxicity of NPC at 12 h without influencing the adhesion molecules. Con clusion: Th1 and Th2 may be involved in regulating liver injury. Th1/Th2 ba lance may critically contribute to the production of the liver injury or re covery from it.