ABSTRACT
Cytokines are low-molecular-weight mediators of cellular communication produced by
multiple cell types in the liver, with the Kupffer cell critically important. Inflammatory
cytokines such as tumor necrosis factor, in-terleukin-1, and interleukin-8, and hepatic
acute-phase cytokines such as interleukin-6 play a role in modulating certain metabolic
complications in alcoholic liver disease and probably play a role in the liver injury
of alcoholic liver disease. Two potential inducers of cytokine production in alcoholic
liver disease are endotoxin and reactive oxygen species generated after ethanol metabolism.
Cytotoxic cytokines likely induce liver cell death by both necrosis and apoptosis
in alcoholic liver disease. Anticytokine therapy has been highly successful in attenuating
cell injury/death in a variety of toxin-induced models of liver injury, including
alcohol-related liver injury. Anticytokine therapy has been used successfully in humans
in disease processes such as Crohn's disease and rheumatoid arthritis. There is an
emerging rationale for use of anticytokine therapy in alcoholic liver disease, with
the goal of maintaining beneficial effects of cytokines and inhibition of the deleterious
effects of these potentially toxic agents.
KEY WORDS
apoptosis - anticytokine therapy - cytokines - cytokine metabolism - cytokine receptors
- Kupffer cells - macrophages - necrosis
