The role of NO in contact hypersensitivity

Contact dermatitis or contact hypersensitivity (CHS) is a common T lymphocyte-mediated allergic disease characterized by local inflammatory skin reactions following contact with small reactive compounds called haptens. In common with other allergic processes, the development of contact dermatitis proceeds in two phases: a sensitization phase which occurs on first exposure to allergen, and an elicitation phase which occurs on subsequent exposure when the clinical manifestations of the disease are observed. This process is hapten-specific, While the pathophysiology of the sensitization phase is well characterized, Our understanding of the elicitation phase is still incomplete, including the relative contribution of the different effector cells and mediators involved. Here we summarize current knowledge of the contribution of nitric oxide (NO) to skin inflammation with special focus on CHS. A number of inflammatory stimuli trigger expression of NO in human and animal skin, and topical application of an NO-releasing cream results in inflammation. Moreover, expression of the inducible isoform of nitric oxide synthase (iNOS) is induced in CHS and iNOS inhibitors injected intradermally suppress CHS responses. However, iNOS-deficient mice develop an aggravated CHS response late in the elicitation phase, suggesting that NO is involved in downregulation of CHS. Based on these data, we propose a comprehensive model of the role of NO in CHS. (C) 2001 Elsevier Science B.V. All rights reserved.