The effect of phototherapy on the dynamics of cytokine mRNA expression in the affected skin of patients with mycosis fungoides

Abstract

   Introduction. The role of the cytokine environment and immune deregulation in the pathogenesis of mycosis fungoides is unquestionable. Despite the fact that one of the methods of therapy for the early stages of mycosis fungoides is phototherapy (PUVA, UVB-311 nm), the effect of ultraviolet radiation on the lymphoproliferative substrate and pathogenetic links in mycosis fungoides has not been fully studied.   Aim: to evaluate the effect of NB-UVB and PUVA therapy on the dynamics of cytokine mRNA expression in the affected skin of patients with mycosis fungoides.   Material and Methods. A comparative non-randomized study of the cytokine mRNA expression dynamics in the affected skin and of the effectiveness of phototherapy was carried out in 28 patients with early stage of mycosis fungoides. The IL4, IL17A, IL17F, and IL22 mRNA expression was determined relative to the endogenous control GAPDH using the real-time reverse transcription PCR (RT-PCR). Evaluation of the effectiveness of NB-UVB and PUVA therapy was carried out using a BSA score (skin lesion area) and a modified severity-weighted assessment tool (mSWAT) score.   Results. The study included 28 patients with early stages (IA–IIA) of mycosis fungoides; 9 patients received NB-UVB and 19 received PUVA therapy. 3.71-fold decrease in mSWAT (p < 0.008), and 3-fold decrease in BSA scores (p < 0.013) were observed in the NB-UVB-treated group. In the PUVA-treated group 3.47- and 2.19-fold lower scores of mSWAT (p < 0.001) and BSA (p < 0.001) were found. There were no significant differences in the expression of the studied cytokines in the NB-UVB-treated group; however, a significant 19 and 72 % increase in IL17F (p = 0.003) and IL22 (p = 0.021) was revealed afterPUVA therapy. Correlation analysis has shown a weak correlation between IL4 and IL17A (r = 0.43, p < 0.027), and IL17F (r = 0.43, p < 0.028) before the treatment. Under the influence of phototherapy, the formation of a cytokine network in the affected skin was observed: there were positive associations between IL4 and IL17A (r = 0.73, p < 0.001), IL17F (r = 0.7, p < 0.001) and IL22 (r = 0.43, p < 0.024); IL17A and IL17F (r = 0.78, p < 0.001); IL22 and IL17A (r = 0.63, p < 0.001) and IL17F (r = 0.66, p < 0.001). In the PUVA-treated group a high negative correlation between IL17A and mSWAT (r = -0.79415, p =0.010586), BSA (r = -0.75432, p = 0.018849) were found.   Conclusion: The positive correlations between IL4, IL17A, IL17F and IL22 in the affected skin of patients with mycosis fungoides may underlie the positive effect of phototherapy.