title: Topically applied nitric oxide induces T-lymphocyte infiltration in human skin, but minimal inflammation.
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-gamma 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-gamma, but not IL-4, was detected in Ze-NO-treated skin (mean control 0.1+/-0.07 pg mg(-1) protein, mean IFN-gamma 0.6+/-0.4 pg mg(-1) protein). We suggest that the potent inflammation induced by acidified NO2(-) is secondary to the release of additional mediators.
authors.affiliation: Department of Dermatology, University of Edinburgh, Edinburgh, UK.
authors.forename: Megan
authors.initials: M
authors.lastname: Mowbray
authors.forename: Xuejing
authors.initials: X
authors.lastname: Tan
authors.forename: Paul S
authors.initials: PS
authors.lastname: Wheatley
authors.forename: Adriano G
authors.initials: AG
authors.lastname: Rossi
authors.forename: Russell E
authors.initials: RE
authors.lastname: Morris
authors.forename: Richard B
authors.initials: RB
authors.lastname: Weller
mesh_terms: D000143:Acids; D000287:Administration, Topical; D001768:Blister / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003872:Dermatitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004890:Erythema / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000009:adverse effects; D007801:Langerhans Cells / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000009:adverse effects; D012883:Skin Ulcer / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D017641:Zeolites / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000143:Acids; D018836:Inflammation Mediators; D020030:Nitric Oxide Donors; D017641:Zeolites; D009569:Nitric Oxide