Parasiticidal effect of δ-aminolevulinic acid-based photodynamic therapy for cutaneous leishmaniasis is indirect and mediated through the killing of the host cells

• Published in: Experimental dermatology 2007-08, Vol.16 (8), p.651-660
• Main Authors: Akilov, Oleg E., Kosaka, Sachiko, O'Riordan, Katie, Hasan, Tayyaba
• Format: Article
• Language: English
• Subjects: aminolevulinic acid; Aminolevulinic Acid - pharmacokinetics; Animals; Biological and medical sciences; Cell Line, Transformed; cutaneous leishmaniasis; Dermatology; Disease Models, Animal; Diseases of the skin. Cosmetics; Ear, External - immunology; Ear, External - parasitology; Human protozoal diseases; Infectious diseases; Interleukin-6 - metabolism; Leishmania major; Leishmania major - drug effects; Leishmania major - growth & development; Leishmania major - immunology; Leishmaniasis, Cutaneous - drug therapy; Leishmaniasis, Cutaneous - immunology; Leshmaniasis; Macrophages - cytology; Macrophages - drug effects; Macrophages - parasitology; Medical sciences; Mice; Mice, Inbred BALB C; Monocytes - cytology; Monocytes - drug effects; Monocytes - parasitology; Parasitic diseases; Photochemotherapy - methods; photodynamic therapy; Photosensitizing Agents - pharmacokinetics; Protoporphyrins - metabolism; Protozoal diseases; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.1600-0625.2007.00578.x

:  Several clinical reports have shown promising, but not optimal, results from photodynamic therapy with δ‐aminolevulinic acid‐derived protoporphyrin IX, termed ALA‐PDT, as a treatment for cutaneous leishmaniasis (CL). Therefore, understanding the basis of the phototoxic response of Leishmania parasites to ALA‐PDT may be critical for optimization. We report here both in vitro and in vivo mechanistic studies of ALA‐PDT against CL. Following in vitro co‐incubation of Leishmania major with 0.1 μm ALA, the PpIX concentration remained at the basal level, whereas after co‐incubation with 0.1 μm exogenous PpIX, the PpIX level was 100‐fold higher. No differences in ALA‐derived PpIX levels were detected between Leishmania‐infected and non‐infected J774.2 cells, and PDT did not demonstrate any parasiticidal effects on amastigotes. In contrast, in vivo topical ALA‐PDT, performed on a murine CL model, resulted in significant reductions of the parasite loads and vigorous tissue destruction. After ALA‐PDT, a dramatically decreased percentage of macrophages and increased levels of interleukin‐6 were observed in the infected skin. The clinical outcome observed with ALA‐PDT is likely the result of unspecific tissue destruction accompanied by depopulation of macrophages rather than direct killing of parasites.