Cytokines and alcoholic liver disease.

It is clear that cytokines cause metabolic disturbances that are similar to known complications of AH. TNF appears to be a proximal mediator of multiple types of experimental liver injury and TNF activity is elevated in ALD, as are the levels of certain other cytokines. On the other hand, low physiologic amounts of cytokines appear to be important for liver regeneration (and perhaps are beneficial to the organism as a whole). Goals for evaluation of anticytokine therapy in ALD will be: (1) determining the timing and type of the particular anticytokine employed (such as, immediate administration of antibody followed by an inhibitor of cytokine production), (2) appropriate monitoring of drug effects on cytokine metabolism as well as liver function and outcome, and (3) maintenance of the regenerative or positive physiologic effects of cytokines while blocking the cytolytic effects. Thus, we predict that ultimate anticytokine therapy will be directed at conserving the positive growth-enhancing effects of cytokines while attenuating their cytolytic effects.