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Prostaglandin E 2 and nitric oxide mediate the acute inflammatory (erythemal) response to topical 5‐aminolaevulinic acid photodynamic therapy in human skin
Author(s) -
Brooke R.C.C.,
Sidhu M.,
Sinha A.,
Watson R.E.B.,
Friedmann P.S.,
Clough G.F.,
Rhodes L.E.
Publication year - 2013
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.12562
Subject(s) - photodynamic therapy , nitric oxide , medicine , prostaglandin e2 , pharmacology , inflammatory response , prostaglandin , dermatology , chemistry , inflammation , immunology , organic chemistry
Summary Background Topical 5‐aminolaevulinic acid photodynamic therapy (5‐ALA‐PDT) causes a clinical inflammatory response in human skin. While histamine mediates the immediate reaction, the mediators of the prolonged erythema are unknown. Objectives To look for involvement of the proinflammatory mediators prostaglandin (PG)E 2 and nitric oxide (NO) in topical PDT‐induced erythema in human skin. Methods A series of studies was performed in healthy volunteers ( n = 35). Following definition of the erythemal time course and dose response to 5‐ALA‐PDT, duplicate 5‐ALA dose series were iontophoresed into the skin of each ventral forearm and exposed to 100 J cm −2 broadband red light. Within subject, arms were randomized to control, or treatment with the cyclooxygenase and NO synthase inhibitors indometacin and N ω ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME), respectively, and the impact on 5‐ALA‐PDT‐induced erythema was quantified. Additionally, release of PGE 2 and NO was directly assessed by sampling dermal microdialysate at intervals following 5‐ALA‐PDT administration. Results A 5‐ALA dose‐related delayed erythema occurred by 3 h ( r = 0·97, P < 0·01), with erythema persisting to 48 h post‐PDT. Topical indometacin applied immediately post‐PDT reduced the slope of erythemal response at 3 h and 24 h ( P < 0·05). Intradermal injection of l ‐NAME into 5‐ALA‐PDT‐treated sites reduced the slope of response at 24 h post‐PDT ( P < 0·001), while significantly inhibiting erythema from 3 h to 48 h post‐PDT ( P < 0·01). Analysis of dermal microdialysate showed release of NO and PGE 2 following treatment. Conclusions Topical 5‐ALA‐PDT upregulates PGE 2 and NO in human skin, where they play a significant role in the clinical inflammatory response. The potential relevance of these mediators to PDT in human cutaneous pathology warrants study.