The role of NO in contact hypersensitivity

Contact dermatitis or contact hypersensitivity (CHS) is a common T lymphocy te-mediated allergic disease characterized by local inflammatory skin react ions following contact with small reactive compounds called haptens. In com mon with other allergic processes, the development of contact dermatitis pr oceeds in two phases: a sensitization phase which occurs on first exposure to allergen, and an elicitation phase which occurs on subsequent exposure w hen the clinical manifestations of the disease are observed. This process i s hapten-specific, While the pathophysiology of the sensitization phase is well characterized, Our understanding of the elicitation phase is still inc omplete, including the relative contribution of the different effector cell s and mediators involved. Here we summarize current knowledge of the contri bution of nitric oxide (NO) to skin inflammation with special focus on CHS. A number of inflammatory stimuli trigger expression of NO in human and ani mal skin, and topical application of an NO-releasing cream results in infla mmation. Moreover, expression of the inducible isoform of nitric oxide synt hase (iNOS) is induced in CHS and iNOS inhibitors injected intradermally su ppress CHS responses. However, iNOS-deficient mice develop an aggravated CH S response late in the elicitation phase, suggesting that NO is involved in downregulation of CHS. Based on these data, we propose a comprehensive mod el of the role of NO in CHS. (C) 2001 Elsevier Science B.V. All rights rese rved.