The role of cytokines in the pathophysiology of chronic liver diseases.

Many of the biological activities of cytokines are similar to clinical manifestations and abnormalities of laboratory parameters observed in chronic liver diseases (CLD). Evidence of impaired cytokine synthesis in CLD comes from studies of serum or plasma levels, supernatants of peripheral blood mononuclear cells stimulated with various agents and from studying cytokine expression locally in the liver. Circulating levels of several cytokine-regulated molecules such as neopterin, soluble IL-2 receptor, adhesion molecules, and metabolites of the nitric oxide pathway are elevated in patients with CLD. Thus inhibition of cytokine synthesis or modulation of their activity could provide not only important information about their pathophysiologic relevance but also have a profound impact on disease progression in CLD. These studies will also show whether prolonged anti-cytokine treatment with interleukin-1- or tumor necrosis factor-inhibitors interferes with host defense mechanism.