THE ROLE OF PROINFLAMMATORY CYTOKINES IN THE PATHOGENESIS OF CHRONIC LIVER-DISEASES

Cytokines are important mediators in the pathogenesis of liver diseases, thus inhibition of their 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. Those studies will also show whether prolonged anti-cytokine treatment does not interfere with host defense mechanisms. There is increasing evidence that inhibition of the final pathway of many cytokines, namely NO with specific antagonists like N-Amino-L-Arginine, increases mortality in animal studies with endotoxin (73). Recently it has also been shown that endogenously synthesized NO prevents endotoxin-induced glomerular thrombosis, proving that some NO is necessary to prevent platelet aggregation (74). Therefore the best approach in most experimental animal and human studies with various liver diseases may be in blocking a single or two cytokines rather than blocking a late effector molecule like NO.