Free radicals in inflammation: second messengers and mediators of tissue destruction

In recent years it has become increasingly apparent that, in man, free radicals play a role in a variety of normal regulatory systems, the deregulation of which may play an important role in inflammation. As examples, we discuss the second messenger roles of: NO in the regulation of vascular tone, O2.- in fibroblast proliferation and H2O2 in the activation of transcription factors such as NF kappa B. Other control mechanisms, the physiological function of which may be perturbed in inflammation, include: the oxidative modification of low density lipoprotein, the oxidative inactivation of alpha-1-protease inhibitor, DNA damage/repair and heat shock protein synthesis. At sites of inflammation, increased free radical activity is associated with the activation of the neutrophil NADPH oxidase and/or the uncoupling of a variety of redox systems, including endothelial cell xanthine dehydrogenase. Although free radicals, thus produced, have the capacity to mediate tissue destruction, either alone or in concert with proteases, we argue that disturbances in the second messenger and regulatory activities of free radicals may also contribute significantly to the inflammatory process.