Mediators of inflammation and acute phase response in the liver.

The acute phase response is a generalized response of the organism to multiple disturbances of its physiological homeostasis. It consists of local and systemic reactions. Inflammatory processes are the main causes for the initiation of these defence mechanisms. Responsible mediators for the acute phase response are predominantly cytokines, whereby the liver is the predominant target organ. Changes in hepatocyte gene expression profiles result in dramatic changes in serum concentrations of specific plasma proteins, called acute phase proteins. IL-6 was identified as the principal mediator of this reaction. Via its cellular signal transducer gp130 IL-6 induces DNA-binding of STAT transcription factors on regulatory elements of target genes. While IL-6 dependent processes are mainly conferred to be protective other inflammatory cytokines are attributed to be cytotoxic for the liver. TNF-alpha was shown to be involved in several models of liver failure as a mediator for both cytotoxicity and cell proliferation. TNF-alpha leads via caspases to the onset of apoptosis, the so-called programmed cell death. On the other hand it activates NF-kappaB thereby triggering inflammatory processes. In this review we display the relevance for intracellular actions of both cytokines in several models of liver injury. Especially we refer to the T-cell mediated Concanavalin A induced liver failure and to liver regeneration induced by CCL4 and partial hepatectomy. Both cytokines contribute in concert to a cellular balance during these pathophysiological conditions.