Analysis of Nitrite and Nitrate in the Study of Inflammation

An acute inflammatory response is mounted in response to a stimulus such as tissue damage or the presence of an invading pathogen (1 ). If this stimulus cannot be removed, then chronic inflammation will develop as classically shown in rheumatoid arthritis (RA). Along with the array of cytokines and chemokines released during inflammation infiltrating macrophages and neutrophils release nitric oxide (NO^• ), which is involved in killing the offending organism (2 ,3 ). Additionally, NO^• is known to mediate the inflammatory response by inhibiting or inducing inflammation via a variety of different pathways (4 –8 ). For example, NO^• has been shown to activate and inhibit the transcription factor, nuclear factor-kappa B (NF-κB) (9). When NO^• activates NF-κB it induces the generation of proinflammatory cytokines such as tumor necrosis factor alpha (TNFα), which are thought to drive the chronic inflammatory response (10 ). However, NO^• can also cause the inhibition of NF-κB by upregulating the production of its inhibitor IκB (11 ,12 ). In a similar way, NO^• has been shown to inhibit neutrophil adhesion, preventing white blood cells (WBC) from infiltrating the site of inflammation (13 ). NO^• also increases the vascular permeability of the vessel wall so that WBCs can reach the affected tissue (14 ). The level of NO^• produced is thought to determine whether NO^• acts as a proinflammatory or antiinflammatory mediator. In many cases, the formation of peroxynitrite, from NO^• and superoxide, is thought to be responsible for some of the proinflammatory actions of NO^• (15 ).