Cytokines and fibrogenesis

Semin Liver Dis. 1999;19(2):129-40. doi: 10.1055/s-2007-1007105.


Cytokines play a major role in the development of hepatic fibrosis, the wound-healing response of the liver to chronic injury. Major concepts in defining the role of cytokines in fibrogenesis include (1) Cytokines may be pro- or antifibrogenic; (2) autocrine, paracrine, and matrix-bound sources of cytokines are the most important; and (3) multiple mechanisms of cytokine regulation are essential to fine-tune their effects. The hepatic stellate cell is the key effector of the fibrotic response and both a principal source and target of cytokines. Activation of stellate cells connotes the conversion of a resting vitamin A-rich cell to one which is proliferative, contractile, fibrogenic, and devoid of vitamin A. The features of stellate cell activation provide a framework in which to understand how cytokines drive fibrosis. These features include (1) proliferation; (2) contractility; (3) fibrogenesis; (4) extracellular matrix degradation; (5) chemotaxis; (6) cytokine release; and (7) retinoid loss. The insights gained from illuminating the role of stellate cells has engendered realistic hopes for treating hepatic fibrosis through modulation of cytokine actions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adipocytes / physiology
  • Animals
  • Cytokines / physiology*
  • Extracellular Matrix / physiology
  • Humans
  • Liver Cirrhosis* / etiology
  • Liver Cirrhosis* / metabolism
  • Liver Regeneration


  • Cytokines