Hepatocyte and immune system: acute phase reaction as a contribution to early defence mechanisms.

Hepatocyte and immune system: acute phase reaction as a contribution to early defence mechanisms Cytokines, a variety of hormone-like molecules, include a group of soluble factors-the interferons, interleukins, and hematopoietic growth factors. They build a complex network of interactive signals and are important for the regulation of hematopoesis and many immune reactions. The interaction of the hepatocyte with the immune system may occur at different levels (Fig 1). For example viral infections often induce interferon (IFN) production, but can also stimulate synthesis of class II molecules, tumour necrosis factor and interleukin (IL) 2.1 2 IFN activates other cytokines directly by interacting with IFN sequence motifs in their promotors.3 Little information exists on the role of cytokines in the initiation and perpetuation of liver diseases. The level and activity of different cytokines such as IL 6 can be abnormal and may contribute to the injury in immunologically mediated liver diseases.4 Another mechanism is the 'acute phase response', in which a panel of cytokines regulates different liver specific genes. There is detailed knowledge on how the signals of these cytokines are transduced from the surface of the hepatocyte membrane to the promotor of the liver specific gene: the mechanisms will be reviewed in this article. Acute phase response and protein The acute phase response has been known for centuries. The ancient Greeks gave an initial description as they observed an increased sedimentation rate of erythrocytes in the blood of severely ill patients.5 Today, we can explain this phenomenon as an increase in the plasma concentration of fibrinogen and other acute phase proteins.6 Most of the acute phase proteins are synthesised in hepatocytes, non-hepatic tissue is only a minor source of the acute phase proteins. Depending on their regulation during inflammation, they are called either positive or negative acute phase proteins. Positive means the plasma concentration is increased and negative means it is decreased during inflammation. In humans the most prominent positive acute phase proteins are C reactive protein (CRP) and serum amyloid A. In man an increase of up to 100 fold is observed during inflammation, whereas in rats the most Acute phase proteins Increase in plasma concentration Decrease in plasma 10-100fold 2-10 fold Up to 2fold concentration Human: C reactive pro-al proteinase Coeruloplasmin Inter a antitrypsin tein inhibitor C3 of comple-Transferrin Serum amlyloid al acid glycoprotein ment al lipoprotein A a} antichymotrypsin a2 antiplasmin Prealbumin Fibrinogen C, inactivator Albumin Haptoglobin Rat: …