Nitric Oxide Functions; an Emphasis on its Diversity in Infectious Diseases

Nitric oxide is a short-lived mediator, which can be induced in a variety of cell types and produces many physiologic and metabolic changes in target cells. It is important in many biological functions and generated from L-arginine by the enzyme nitric oxide synthase. Nitric oxide conveys a variety of messages between cells, including signals for vasorelaxation, neurotransmission and cytotoxicity. In macrophages, nitric oxide synthase activity appears slowly after exposure of the cells to cytokines and bacterial products, is sustained, and functions independently of calcium and calmodulin. The cytokine- inducible nitric oxide synthase (iNOS) is activated by several immunological stimuli, leading to the production of large quantities of nitric oxide which can be cytotoxic. To date, there have been conflicting reports concerning the clinical significance of nitric oxide in infections. Some authors have proposed that nitric oxide contributes to the development of severe and complicated cases, while others have argued that nitric oxide has a protective role. The aim of this review is to evaluate the functions of nitric oxide production toward oxidative stress induced by infections or inflammations. It is indicated that NO is an important, but possibly not essential contributor in the control of acute phase of infections and it is only part of an immunopathological chain against pathogens. The anti-microbial function does not relate only to nitric oxide action or its related molecules, a combination of nitric oxide and immune factors is required to resolve pathogenic micro-organisms. Consequently, the NO theory in infectious diseases may lead to the novel ideas for therapy and prevention.