Impact of etanercept treatment on ultraviolet B-induced inflammation, cell cycle regulation and DNA damage.
BACKGROUND
Current studies indicate that treatment with tumour necrosis factor (TNF)-α blockers plus ultraviolet (UV) B phototherapy results in higher relative Psoriasis Area and Severity Index reduction as compared with TNF-α monotherapy.


OBJECTIVE
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-α.


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-α blockers might increase the risk of photocarcinogenesis by influencing apoptotic as well as antiapoptotic pathways.
Department of Dermatology, Ruhr-University Bochum, Bochum, Germany. t.gambichler@klinikum-bochum.de
T
T
Gambichler
C
C
Tigges
A
A
Dith
M
M
Skrygan
N
N
Scola
P
P
Altmeyer
A
A
Kreuter
D000328:Adult; D001706:Biopsy; D002453:Cell Cycle / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D004890:Erythema / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*
D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept