REGULATION OF INFLAMMATORY AND ALLERGY RESPONSES BY ANTI-LFA-1 MONOCLONAL ANTIBODY

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In this project, we demonstrated that mouse liver injury model induced by propionibacterium acnes (P.acnes) plus LPS is T cell-dependent one judging from the experiment using T cell deficient nude mice. Because the liver injury was completely blocked by anti-LFA-1 mAb, LFA1-ICAM-1 interaction is essential for the activation and migration of effector cells to liver. It was also demonstrated that Th1-activating cytokine, IFN-gamma and IL-12 are key cytokines in this liver injury model. C57BL/6 mice, which are prone to show Th1 immunity, are sensitive to P.acnes plus LPS-induced liver injury, while BALB/c showing Th2 immunity are resistant to this. Therefore, genetically-controlled Th1/Th2 balance appeared to be important factor the induction of liver injury.The important role of LFA-1 molecule in allergy is also demonstrated from the evidence that anti-LFA-1 mAb administration inhibited IgE production in vivo for long-term.Thus, the important role of LFA-1 molecule and Th1-Th2 balances in the regulation of liver inflammatory responses and allergy was clearly demonstrated by this project.