Inhibition of inflammatory liver injury by a monoclonal antibody against lymphocyte function-associated antigen-1.

When mice were given an i.v. injection of LPS 7 days after an i.v. injection of Propionibacterium acnes, liver injury and a rapid increase of serum alanine aminotransferase and asparagine acid aminotransferase occurred. The in vivo administration of mAb against LFA-1 on days 1, 2, and 3 after the i.v. injection of P. acnes resulted in a potent inhibition of all these dysfunctions. Using P. acnes and the LPS model, we found that anti-LFA-1 mAb protected the mice from P. acnes and LPS-induced lethal shock. During the course of P. acnes and LPS-induced liver injury, inflammatory cells infiltrated the liver and caused a massive hepatic cell necrosis. Flow cytometry revealed that the liver-infiltrating cells were mainly leukocytes expressing a higher level of LFA-1 antigen than that seen in the normal liver. These results suggested that the LFA-1 molecule on liver-infiltrating leukocytes may play an important role in the induction of inflammatory liver injury.