Cytokines in pathogenesis of alcohol-induced hepatitis and therapeutic options
Abstract
The aim of review. To discover the role of cytokines in pathogenesis of severe alcohol-induced hepatitis and to show directions for therapeutic action.
Original positions. Cytokines is aggregative term including various groups of biologically active substances: interleukins, tumor necrosis factor-α family (TNF-α), interferons, chemokines, growth factors, for example, transforming growth factor-β (TGF-β), colony-stimulating factors, etc. Now the key role of some cytokines in alcoholinduced damage of liver is proved. Such clinical signs of disease, as loss of body weight, cholestasis, fibrosis, hypergammaglobulinemia, production of acute-phase proteins are attributed to cytokines action. Interleukin-6 and TNF-α are involved in development of cholestasis and synthesis of acute-phase proteins. The first pathophysiological event at alcoholic damage of liver is TNF-α production which stimulates synthesis of other cytokines. The latter participate in recruitment of inflammatory cells to damage zone that results in hepatocytes destruction. At the same time reparative processes including fibrogenesis are initiated as well. In patients with progressing damage of the liver the balance between proinflammatory and anti-inflammatory cytokines shifts towards the first, that interferes with natural body control over inflammation and fibrogenesis. The hypothesis of “double impact” in progression of fatty liver disease, including its alcoholic variant is proposed. In treatment of severe alcohol-induced hepatitis glucocorticosteroids, inhibitors of cytokine synthesis and anti-cytokine antibodies, ursodeoxycholic acid are applied to suppress redundant production of proinflammatory cytokines. Clinical case demonstrating efficacy of combined treatment of the patient with severe alcoholic hepatitis is presented.
Conclusion. Alcohol-induced hepatitis with disorders of liver function is related to one of the most severe forms of alcoholic liver disease associated to high intrahospital mortality. The leading part in its pathogenesis belongs to proinflammatory cytokines, first of all – to TNF-α. Treatment of this liver damage assumes influence on basic pathogenic links.
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Review
For citations:
Mayevskaya M.V., Buyeverov A.O. Cytokines in pathogenesis of alcohol-induced hepatitis and therapeutic options. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2009;19(2):14-19. (In Russ.)
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