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

ABSTRACT

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)E2 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 Nω -nitro-l-arginine methyl ester (l-NAME), respectively, and the impact on 5-ALA-PDT-induced erythema was quantified. Additionally, release of PGE2 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 PGE2 following treatment. CONCLUSIONS: Topical 5-ALA-PDT upregulates PGE2 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.