EDITORIAL Nitric oxide in rheumatology Christophe Bernardeau 1,2 , Emmanuelle Dernis-Labous 1 , Hervé Blanchard 1 , Dominique Lamarque 3 , Maxime Breban 1,4 * 1 Inserm U477, hôpital Cochin, université René-Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; 2 Rheumatology department, hôpital Lariboisière, 2, rue Ambroise-Paré, 75475 Paris cedex 10, France; 3 Inserm U99 and Gastroenterology department, hôpital Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France; 4 Rheumatology institute, hôpital Cochin, université René-Descartes, 27, rue du Faubourg-Saint- Jacques, 75014 Paris, France (Submitted for publication April 27, 2000; accepted in revised form April 11, 2001) Summary – Nitric oxide (NO) is attracting considerable interest because it mediates many functions. This gas is ubiquitously produced in the body by three enzymes, called NO synthases. Two NO synthases are constitutively expressed, one in the nervous system and the other in the blood vessels, where it regulates tissue perfusion. The third NO synthase can be induced by several stimuli (bacterial endotoxins, cytokines), most notably in inflammatory cells and chondrocytes. The effects of NO produced by the inducible NO synthase range from T-cell response modulation to formation of free radicals responsible for tissue damage and cartilage matrix degradation. Administration of NO synthase inhibitors in animal models of arthritis yields ambiguous effects, often with prevention of arthritis, but sometimes with worsening of established arthritis. The data available to date do not support the use of such inhibitors in the treatment of human arthritis. Joint Bone Spine 2001 ; 68 : 457-62. © 2001 Éditions scientifiques et médicales Elsevier SAS animal arthritis models / inflammation / nitric oxide / NO synthase / osteoarthritis INTRODUCTION In 1916, Mitchell et al. reported the first evidence that mammalians produce nitrates [1]. Only 61 years later, in 1987, was the source of these nitrates identified as nitric oxide (NO), or endothelium-derived relaxing factor (EDRF). Since then, interest in NO has grown in many fields of biomedical research [2, 3]. An early finding was that NO is involved in inflammation related to any cause (infections, immunological disorders, or tumors). NO was selected as the molecule of the year in 1992 by the journal Science [4-6]. However, despite the increasing fund of experimental data suggesting a role for NO in human diseases, it is often difficult to deter- mine whether NO is beneficial or deleterious in the systems studied to date [4, 7, 8]. SOURCES OF NO NO, a gas with a molecular weight of 30 daltons, diffuses freely through cell membranes and has a half- life of only a few seconds [6, 9]. L-arginine is converted to NO by several enzymes, called NO synthases (NOSs), which are related to the P450 cytochromes and whose active form is homodimeric [10-12]. Three NOS iso * Correspondence and reprints. Joint Bone Spine 2001 ; 68 : 457-62 © 2001 Éditions scientifiques et médicales Elsevier SAS. All rights reserved S1297319X01003086/EDI