Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure

The hepatitis C virus (HCV) encodes approximately 10 different structural and non-structural proteins, including the envelope glycoprotein 2 (E2). HCV proteins, especially the envelope proteins, bind to cell receptors and can damage tissues. Endothelial inflammation is the most important determinant of fibrosis progression and, consequently, cirrhosis. The aim of this study was to evaluate and compare the inflammatory response of endothelial cells to two recombinant forms of the HCV E2 protein produced in different expression systems (Escherichia coli and Pichia pastoris). We observed the induction of cell death and the production of nitric oxide, hydrogen peroxide, interleukin-8 and vascular endothelial growth factor A in human umbilical vein endothelial cells (HUVECs) stimulated by the two recombinant E2 proteins. The E2-induced apoptosis of HUVECs was confirmed using the molecular marker PARP. The apoptosis rescue observed when the antioxidant N-acetylcysteine was used suggests that reactive oxygen species are involved in E2-induced apoptosis. We propose that these proteins are involved in the chronic inflammation caused by HCV.

Syndrome of malnutrition-inflammation complex in chronic alcoholics.

Several studies have reported elevated serum ferritin levels in patients of chronic alcohol abuse. We hypothesized that serum ferritin may be acting as a marker of acute phase reactant, reflecting the inflammatory status of patients of chronic alcohol abuse, rather than as a marker of iron overload . Hence we correlated serum ferritin levels with interleukin 6 (IL-6), interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF -α ) which are markers of inflammation. Serum ferritin and IL-6 levels were significantly elevated at the time of admission. The elevation of IL-6 correlated well with the increase in ferritin levels (r=0.78, p<0.01). Serum iron levels were not significantly different before and after abstinence from alcohol. We also speculated that the inflammatory status was associated with the malnutrition that is observed in alcohol abuse. Therefore we studied serum total protein, albumin, prealbumin and transferrin levels as markers of nutrition in patients of chronic alcohol abuse. Serum levels of all these nutritional parameters increased significantly after 8 weeks of abstinence from alcohol and were accompanied by reduced levels of ferritin and IL-6. Hence it is possible that a malnutrition inflammation complex like syndrome exists in patients of alcohol abuse.