ABSTRACT
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 antifibrogenie; (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.
KEY WORDS
stellate cells - fibrogenesis - receptors
