Immunosuppressive effects of photodynamic therapy by topical aminolevulinic acid.

Photodynamic therapy (PDT) has been used for inflammatory skin disorders as well as superficial skin cancers such as solar keratosis and Bowen's disease. Whether PDT with topical application of aminolevulinic acid (ALA) and exposure to visible light has a similar immunosuppressive action to ultraviolet phototherapy was investigated using a murine contact hypersensitivity (CHS) model. The number of epidermal Langerhans cells (LC) was decreased with their morphological changes 1 day after PDT with the minimal level at 5 days and gradual recovery thereafter. Conversely, the number of CD11c(+) I-A(+) cells was significantly increased in the draining lymph nodes after PDT. This suggests that LC moved from PDT-treated skin, resulting in the decrement of epidermal LC and migration to lymph nodes. CHS response to DNFB applied on the PDT-treated skin with 20% ALA and 40 J/cm(2) visible light was significantly suppressed (local immunosuppression). When mice were treated with 80 J/cm(2) of PDT, CHS response to the antigen applied on untreated distant skin was also significantly suppressed (systemic immunosuppression). The locally or systemically immunosuppressed mice by PDT were attempted to sensitize again with DNFB on non-treated skin, but elicitation responses were significantly suppressed. However, these mice were able to be sensitized with another hapten, oxasolone. Thus, a hapten-specific immunological unresponsiveness (tolerance) was induced in mice by topical ALA-PDT. These findings suggest that PDT has a potential immunological contribution to clinical efficacy for inflammatory diseases identical to ultraviolet phototherapies.

Therapeutic and prophylactic effects of PUVA photochemotherapy on atopic dermatitis-like lesions in NC/Nga mice.

BACKGROUND: Psoralens and ultraviolet A radiation (PUVA) photochemotherapy has been used for severe cases of atopic dermatitis (AD). To understand the mechanisms of action is important for the choice of treatments. AD-like lesions can be induced experimentally in NC/Nga mice. OBJECTIVES: To evaluate clinically and histologically the therapeutic and prophylactic effects of PUVA on AD-like dermatitis using NC/Nga mice. METHODS: PUVA therapy was performed with intraperitoneal injection of 4 mg/kg of 8-methoxypsoralen (8-MOP) and 4 J/cm(2)-UVA irradiation before and after development of AD-like lesions in NC/Nga mice which had been maintained in a conventional room (Conv-NC/Nga mice). Clinical skin conditions were evaluated periodically by a clinical severity score defined. Lesions were histologically examined in haematoxylin-eosin or toluidine blue-stained sections. Plasma levels of total IgE were measured at various time points. RESULTS: In Conv-NC/Nga mice infested with mite, AD-like lesions started to develop at 8 week of age and thereafter increased in severity score. PUVA therapy at lower does than minimal phototoxic dose suppressed the development of dermatitis and was also therapeutically effective against established lesions. Proliferation of dermal mast cells in AD-like lesions was suppressed, but IgE hyperproduction was not changed after PUVA. CONCLUSIONS: These observations suggest that PUVA photochemotherapy reveals not only therapeutic but also prophylactic effects on human AD.