ABSTRACT
Tissue injury induces an inflammatory response characterized by an accumula tion of macrophages and neutrophils at sites of damage. These cells release proinflammatory cytokines and cytotoxic mediators to destroy invading pathogens and initiate tissue repair. However, recent studies have demonstrated that these mediators, which include pro-inflammatory cytokines, bioactive lipids, hydro lytic enzymes, and reactive oxygen and nitrogen intermediates, may also con tribute to tissue damage (1-4). This process involves both direct damage to target tissue and amplification of the inflammatory response. Among the macrophagederived mediators implicated in toxicity, nitric oxide has recently received con siderable attention. It is reportedly produced in excess quantities during tissue injury associated with inflammation (5-7). Moreover, in various experimental models, modulating nitric oxide production modifies tissue injury. Whether nitric oxide plays a protective or pathological role in tissue injury appears to vary with the toxicant, the target tissue, and the extent to which toxicity is mediated by reactive oxygen intermediates. In this chapter, we review evidence implicating nitric oxide in liver and lung injury.
