AB0186 High-dose narrowband ultraviolet a1 induces the regression of dermal fibrosis in animal model of scleroderma

Background Ultraviolet A1 (UVA1) phototherapy implications for systemic sclerosis still remain area of research. The wide spectral waveband of UVA1 could react with many chromophores in the skin, leading to different effects of the immune system.1 In accordance with the physical properties of UVA1 and the optical features of the skin, the narrowband UVA1 would influence collagen metabolism with a reduced chance of side effects. None of the previously conducted studies evaluated the effectiveness of narrowband UVA1 on dermal fibrosis. Objectives The main objective of the present study was to define the impact of high-dose of 365±5 nm UVA1 on the dermal thickness in pre-established, bleomycin-induced mouse model of scleroderma. Methods Forty two DBA/2 line mice were randomly divided into the following 6 groups (7 animals in each): group I– mice injected with sodium chloride (NaCl) for 3 weeks; group II – mice injected with bleomycin (Bleo) for 3 weeks; group III – mice injected with NaCl for 8 weeks; group IV – mice injected with Bleo for 3 weeks and then with NaCl for 5 weeks; group V – mice injected with Bleo for 8 weeks; group VI – mice injected with Bleo for 8 weeks and parallel treated with average cumulative dose of 1200 J/cm2 of UVA1 for the last 5 weeks (the treatment group). Light source emitting a narrow band UVA1 of 365±5 nm and 21 mW/cm2; power density was used in the study. Histological analysis was performed for the evaluation of dermal thickness. The Mann – Whitney U test was used for statistical analysis. Results After bleomycin injections that spanned a period of 3 and 8 weeks, the dermal thicknesses were significantly (p=0.002) higher (group II – 433.69±54.37 µm and group V – 497.43±57.83 µm, respectively) as compared to that of the healthy controls (group I – 166.04±25.29 µm and group III – 178.18±42.35 µm, respectively). The 3 weeks of bleomycin injections and the following 5 weeks of NaCl did not cause any spontaneous regression of dermal fibrosis (group IV – 443.87±41.77 µm; group II – 433.69±54.38 µm; p=0.482). Dermal thickness in mice injected with bleomycin for 8 weeks and irradiated with UVA1 for the last 5 weeks was significantly lower than that in mice challenged only with bleomycin for 8 weeks (group VI – 253.96±31.83 µm and group V – 497.43±57.83 µm, respectively; p=0.002). Furthermore, treatment with 1200 J/cm2 of UVA1 in parallel with profibrotic stimulus of bleomycin resulted in a lower dermal thickness as compared with pre-existing fibrotic changes in the group IV observed after 3 weeks of bleomycin injections (group VI – 253.96±31.83 µm and group IV – 443.87±41.77 µm; p=0.002) (figure 1). Conclusions The cumulative dosage of 1200 J/cm2 of narrowband UVA1 not only prevented the progression of dermal fibrosis, but also induced the regression of pre-existing fibrotic changes in bleomycin-induced mouse model of scleroderma. Reference [1] Matthews YJ, Halliday GM, Phan TA, Damian DL. Wavelength dependency for UVA-induced suppression of recall immunity in humans. J Dermatol Sci2010;59(3):192–7. Acknowledgements For the funding by the World Federation of Scientists Lithuanian National Scholarship Program. Disclosure of Interest None declared