Cytokines and Renin-Angiotensin System Signaling in Hepatic Fibrosis

Hepatic fibrosis is the result of a complex interplay between resident hepatic cells, infiltrating inflammatory cells, and a number of locally acting peptides called cytokines. Key mediators include transforming growth factor b1, vasoactive substances, adipokines, inflammatory cytokines and chemokines. Angiotensin II, the main effector of the renin-angiotensin system, is a true cytokine that plays a major role in liver fibrosis. Angiotensin II is locally synthesized in the injured liver and induces profibrogenic actions in hepatic stellate cells. Drugs blocking the renin-angiotensin system are promising antifibrotic agents. There are multiple signal transduction pathways involved in cytokine signaling. Drugs interfering intracellular pathways involved in increased collagen production are potential therapies for liver fibrosis.