PILOT STUDY--CYTOKINE MODULATION OF ACUTE LIVER INJURY

The long-term objective of this project is to delineate the role of various cytokines in acute liver injury, regeneration, and repair. The following questions will be addressed. (1) What is the role of transforming growth factor-Beta (TGF-Beta) and tumor necrosis factor (TNF) in acute hepatic damage, regeneration and repair? This work will involve the examination of two models of acute liver injury, CC1 4 and galactosamine-induced liver damage, and regeneration after partial hepatectomy. Changes in TGF-Beta and TNF gene expression will be analyzed by Northern blot hybridizations and nuclear run-on assays, and protein levels quantitated as well. (2) What are the effects of inhibiting the actions of TGF-Beta and TNF? TGF- Beta and TNF blocking antibodies will be administered to the animal models which will then be studied for changes in histology, gene expression, or survivability. (3) How do prostaglandin PGE 2 and dexamethasone affect liver injury and repair? PGE 2 and dexamethasone will be used in the in vivo models to determine these agents effects on acute liver injury and repair. By achieving these aims a better understanding of the mechanisms of acute liver injury and repair will exist. With this basic knowledge, proper therapeutic modalities for this entity will become apparent.