INFLAMMATION, FREE-RADICALS, AND ANTIOXIDANTS

It is becoming increasingly apparent that certain types of inflammator y 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 inva de the tissue. These reactive radicals and oxidants may injure cells a nd tissue directly via oxidative degradation of essential cellular com ponents as well as injure cells indirectly by altering the protease/an tiprotease balance that normally exists within the tissue interstitium . It is becoming increasingly apparent that in addition to promoting c ytotoxicity, reactive oxygen metabolites may also initiate and/or ampl ify inflammation via the upregulation of several different genes invol ved in the inflammatory response, such as those that code for proinfla mmatory cytokines and adhesion molecules. This may occur by the activa tion of certain transcription factors, such as nuclear transcription f actor kB (NF-kB). NF-kB is a ubiquitous transcription factor and pleio tropic regulator of numerous genes involved in the immune and inflamma tory response. Essential nutrients such as vitamins C and E may protec t against oxidant-mediated inflammation and tissue damage by virtue of their ability to scavenge free radicals and by their ability to inhib it the activation of NF-kB (and possibly other oxidant-sensitive trans cription factors). Thus, maintaining adequate antioxidant status may p rovide a useful approach in attenuating the cellular injury and dysfun ction observed in some inflammatory disorders.