Topically applied nitric oxide induces T-lymphocyte infiltration in human skin, but minimal inflammation.
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.
Mowbray
Megan
M
Department of Dermatology, University of Edinburgh, Edinburgh, UK.
Tan
Xuejing
X
Wheatley
Paul S
PS
Rossi
Adriano G
AG
Morris
Russell E
RE
Weller
Richard B
RB
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
D000143:Acids; D018836:Inflammation Mediators; D020030:Nitric Oxide Donors; D017641:Zeolites; D009569:Nitric Oxide