Synthesis of acute phase proteins in rats with cirrhosis exposed to lipopolysaccharide

We examined the acute phase response induced by intraperitoneal injection of a low dose of LPS, in sham operated control animals and in rats with liver cirrhosis induced by bile duct ligation (BDL). We measured the serum concentrations of the most important acute phase proteins and their liver tissue gene expressions, assessed by mRNA levels. The BDL-model itself increased the serum concentration of α1-acid glycoprotein (α1AGP) and haptoglobin. LPS was lethal to 25% of the cirrhotic animals and to none of the controls. Twenty-four hours after LPS, the serum concentration of α1AGP and haptoglobin, the mRNA level of these acute phase proteins and of α2-macroglobulin and thiostatin rose to the same level in the animals with cirrhosis and in controls.In rats with experimental cirrhosis LPS caused high mortality. In the survivors, the cirrhotic liver still synthesized acute phase proteins as the normal liver, indicating a normal hepatic contribution to this part of the acute phase response.Liver cirrhosis is associated with a high frequency of bacterial infections that increases mortality [1]. The first year after being diagnosed with cirrhosis, patients suffer a more than 40-fold increased mortality from infection compared with the adjusted background population [2]. This reflects multiple immunologic abnormalities secondary to cirrhosis. Attention has focused particularly on the innate immune system, the many protein components of which are synthesized by the liver itself [3]. Thus, it is a frequently held notion that the acute phase response is compromised in cirrhosis patients. However, studies on this subject are few [4,5] and it has not been yet systematically examined in either cirrhosis patients or in experimental models.The acute phase response consists of changes in the serum concentration of multiple proteins due to a reorganization of hepatic protein synthesis favouring "the acute phase proteins" and decreasing the so-called "negative acute phase proteins". T