Impact of etanercept treatment on ultraviolet B-induced inflammation, cell cycle regulation and DNA damage

P>Background Current studies indicate that treatment with tumour necrosis factor (TNF)-alpha blockers plus ultraviolet (UV) B phototherapy results in higher relative Psoriasis Area and Severity Index reduction as compared with TNF-alpha monotherapy. Objectives This study aimed to investigate the acute impact of etanercept on UVB-induced inflammation, cell cycle regulation and DNA damage. Methods Eleven subjects diagnosed with psoriasis who fulfilled the indication criteria for etanercept treatment were studied. A healthy skin site on the upper back was treated with UVB at 2 minimal erythema doses (MED). After 1, 24 and 72 h punch biopsies were taken from this site. Following the 72 h biopsy etanercept 50 mg was administered subcutaneously. After 48 h, 2 MED was given on healthy skin adjacent to previously treated skin sites. Again, after 1, 24 and 72 h punch biopsies were taken from this site. UVB- as well as UVB plus etanercept-treated skin was assessed by means of colorimetry and immunohistochemical studies for caspase 3, cyclin D-1, interleukin-12, Ki-67, p16, p53, survivin, thymine dimers and TNF-alpha. Results Erythema formation did not differ significantly between UVB- and UVB plus etanercept-treated sites. Comparisons between UVB- and UVB plus etanercept-treated sites at a given time (1, 24, 72 h) did not result in significant differences in immunoreactivity of the markers investigated, except for cyclin D-1, p53 and survivin. Immunoreactivity of cyclin D-1 and p53 was significantly decreased in UVB plus etanercept-treated sites at 24 h. Survivin expression was significantly higher in UVB plus etanercept-treated skin as compared with UVB monotherapy. Conclusions Our data indicate that combined treatment with broadband UVB and TNF-alpha blockers might increase the risk of photocarcinogenesis by influencing apoptotic as well as antiapoptotic pathways.