Prostaglandin E2 and nitric oxide mediate the acute inflammatory (erythemal) response to topical 5-aminolaevulinic acid photodynamic therapy in human skin

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-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 3h (r=0 center dot 97, P<0 center dot 01), with erythema persisting to 48h post-PDT. Topical indometacin applied immediately post-PDT reduced the slope of erythemal response at 3h and 24h (P<0 center dot 05). Intradermal injection of l-NAME into 5-ALA-PDT-treated sites reduced the slope of response at 24h post-PDT (P<0 center dot 001), while significantly inhibiting erythema from 3h to 48h post-PDT (P<0 center dot 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.