Inflammation, free radicals, and antioxidants.

It is becoming increasingly apparent that certain types of inflammatory tissue injury are mediated by reactive oxygen metabolites. The most likely sources of these oxidizing agents are the phagocytic leukocytes (e.g., neutrophils, monocytes, macrophages, and eosinophils) that invade the tissue. These reactive radicals and oxidants may injure cells and tissue directly via oxidative degradation of essential cellular components as well as injure cells indirectly by altering the protease/ antiprotease balance that normally exists within the tissue interstitium. It is becoming increasingly apparent that in addition to promoting cytotoxicity, reactive oxygen metabolites may also initiate and/or amplify inflammation via the upregulation of several different genes involved in the inflammatory response, such as those that code for proinflammatory cytokines and adhesion molecules. This may occur by the activation of certain transcription factors, such as nuclear transcription factor kB (NF-kB). NF-kB is a ubiquitous transcription factor and pleiotropic regulator of numerous genes involved in the immune and inflammatory response. Essential nutrients such as vitamins C and E may protect against oxidant-mediated inflammation and tissue damage by virtue of their ability to scavenge free radicals and by their ability to inhibit the activation of NF-kB (and possibly other oxidant-sensitive transcription factors). Thus, maintaining adequate antioxidant status may provide a useful approach in attenuating the cellular injury and dysfunction observed in some inflammatory disorders.