[NO, ambivalent effector of non-specific immunity and of inflammation]

Nitric oxide produced from the amino acid L-arginine is a short-lived free radical produced by many types of cells for a variety of biological functions, including defence against a range of pathogens. NO synthesis via NOS-2 is deeply intertwined in the cytokine network. Thus, expression of NOS-2 is induced by IFN-gamma, TNF and IL-1 as well as microbial products whereas IL-4, IL-10 and TGF-beta down-regulate its synthesis. In spite of this tight regulation, excessive production of NO as a result of immunological stimulation via NOS-2 could have potential toxic effects on hosts. Indeed, large amount of nitric oxide (NO) are produced at sites of inflammation through the action of NOS-2. The role of NO in inflammation is unclear and may depend on the balance between NO and O2-. The somewhat paradoxical effects of NO might indeed be explained by its various chemical forms. Besides, understanding the regulation and function of NOS-2 is likely to lead to therapeutic approaches to treat a number of diseases.