Anti-TNF agent etanercept augments UV-induced skin cancer development in SKH-1 mice

Abstract

Background

Despite being employed in the treatment of inflammatory disorders for more than 20 years all over the world, data regarding photocarcinogenic risks of anti-TNF agents is scarce.

Objective

To assess photocarcinogenic potential of anti-TNF agents.

Methods

This was a placebo controlled, split-body (UVB-treated versus -untreated) study on mice. Treatment groups were infliximab (n = 11), etanercept (n = 11), cyclosporine (n = 11) and vehicle control (n = 11). Agents were introduced on the 10th week of phototherapy and continued through 24th week. The macroscopic, histological and immunohistochemical analysis of test sites were carried out.

Results

Overall 132 tumors were detected on test sites. All of these tumors developed on UV-exposed sides. Histologic examination of these tumors was compatible with keratinocytic neoplasia in 128, mastocytosis in 3, epidermal cyst in 1. Median tumor burden in the UVB exposed areas for ETN, IFX, CYC, and control groups were 14.91, 10.20, 6.28, and 3.14 cm², respectively. ETN group demonstrated both higher tumor burden and keratinocytic neoplasia numbers than controls (p = .03, p = .025). Although there were 1.8 and 1.7 times more keratinocytic neoplasms in IFX and CYC groups compared to controls, these differences didn’t reach statistically significant levels (p = .14; p = .19).

Conclusion

This study points out to a significant photocarcinogenic potential of anti-TNF agent etanercept.

Keywords:

• Photocarcinogenesis
• cyclosporine
• psoriasis
• immunosuppression

Ethical approval

This study was approved by former Gülhane Military Medical Academy Animal Experimentation Local Ethics Committee (0830-25-14).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study is supported by Gülhane (formerly Gülhane Military Medical Academy) Research Grant Committee.