Immune cells: free radicals and antioxidants in sepsis

The excessive production of reactive oxygen species (ROS), associated with inflammation, leads to a condition of oxidative stress. Oxidative stress is a major contributing factor to the high mortality rates associated with several diseases such as endotoxic shock. This condition can be controlled to a certain degree by antioxidant therapies. Immune cells use ROS in order to support their functions and therefore need adequate levels of antioxidant defenses in order to avoid the harmful effect of an excessive production of ROS. This review discusses the toxic effects of endotoxin, paying particular attention to immune function. It continues by analyzing the mechanism to which specific cells of the immune system recognize endotoxin, and the resulting pathways leading to nuclear Factor-kappaB activation and proinflammatory gene transcription. We also focus on the involvement of reactive oxygen and nitric oxide (NO) and the protective role of antioxidants. The potential clinical use of antioxidants in the treatment of sepsis and the effects on the redox state of the immune cells are discussed. (C) 2004 Elsevier B.V All rights reserved.