Nitric oxide in inflammation and immune response

This short review deals with the role of a recently found signalling molecule, nitric oxide (NO), in inflammatory and immune responses. NO regulates inflammatory erythema and oedema and has cytotoxic action against micro-organisms. In some instances (such as reperfusion injury) NO has cytoprotective properties. Production of large amounts of NO by activated macrophages accounts for their ability to suppress lymphocyte proliferation. NO synthesis in lymphocytes is questionable but cytokines secreted by activated lymphocytes regulate NO synthesis by macrophages. Constitutive NO synthase is activated in neutrophils in response to inflammatory stimuli and NO has diverse, often biphasic effects on neutrophil functions. Increased concentrations of nitrite and nitrate (metabolites of NO) are present in arthritic joints. NO is synthesized not only by migrated inflammatory cells but also by articular chondrocytes and inflamed synovial membrane. In the inflamed joint, NO regulates the synthesis of several inflammatory mediators and functions of inflammatory cells. In addition, NO seems to mediate some destructive effects of proinflammatory cytokines such as interleukin-1. In conclusion, NO regulates several humoral and cellular responses in inflammation, having both anti-inflammatory and proinflammatory properties depending on the type and phase of the inflammatory reaction.