1. ¹Department of Dermatology, University of Edinburgh, Edinburgh, UK
2. ²EaStChem School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, UK

Correspondence: Dr Richard B. Weller, Department of Dermatology, University of Edinburgh, Lauriston Building, Lauriston Place, Edinburgh EH3 9HA, UK. E-mail: r.weller@ed.ac.uk

³These authors contributed equally to this work.

Received 12 March 2007; Revised 21 June 2007; Accepted 1 August 2007; Published online 4 October 2007.

Abstract

Nitric oxide (NO) plays an important role in the cutaneous response to UV radiation and in cutaneous inflammation. The presence of inducible NO synthase protein in a number of inflammatory dermatoses, coupled with the induction of an intense cutaneous inflammatory infiltrate following topical application of the NO donor-acidified nitrite (NO₂^-), has set the paradigm of NO being an inflammatory mediator in human skin. Using zeolite NO (Ze–NO), a chemically inert, pure NO donor, we have shown that NO per se produces little inflammation. Biologically, relevant doses of Ze–NO induce a dermal CD4-positive T-cell infiltrate and IFN- secretion. In contrast acidified nitrite, releasing equal quantities of NO (measured by dermal microdialysis and cutaneous erythema), induces an intense epidermal infiltrate of macrophages with a similar dermal infiltrate of CD3-, CD4-, CD8-, and CD68-positive cells and neutrophils. Suction blisters were created in Ze–NO-treated and control skin. IFN-, but not IL-4, was detected in Ze–NO-treated skin (mean control 0.10.07 pg mg^-1 protein, mean IFN- 0.60.4 pg mg^-1 protein). We suggest that the potent inflammation induced by acidified NO₂^- is secondary to the release of additional mediators.