Secukinumab and metformin ameliorate dermal fibrosis by decreasing tissue interleukin-17 levels in bleomycin-induced dermal fibrosis

Abstract

Although the pathogenesis of systemic sclerosis is not exactly known, it is thought that immune activation has prominent roles in pathogenesis. Secukinumab is a monoclonal antibody against interleukin (IL)-17A. Metformin, a widely used antidiabetic medication, has anti-proliferative, immunomodulating and anti-fibrotic activities. The purpose of our study is to determine the therapeutic efficacy of secukinumab and metformin on bleomycin (BLM) induced dermal fibrosis. Fifty Balb/c female mice were divided into 5 groups: (group 1 control, 2 sham, 3 secukinumab, 4 metformin and 5 secukinumab + metformin). The mice in the control group received 100 mu L phosphate-buffered saline (PBS), while the mice in other groups received 100 mu L (100 mu g) BLM in PBS subcutaneously (sc) every day for 4 weeks. In addition, mice in groups 3 and 5 received secukinumab at a dose of 10 mg/kg/wk sc, and mice in the groups 4 and 5 received oral metformin 50 mg/kg/d for 28 days. All groups of mice were sacrificed at the end of the 4th week and tissue samples were taken for analysis. In addition to histopathological analysis, skin tissue messenger RNA (mRNA) expressions of IL-17 and collagen 3A were measured by real-time polymerase chain reaction. Repeated BLM injections had caused dermal fibrosis. In addition, the mRNA expressions of IL-17 and collagen 3A were increased in the BLM group. Secukinumab and metformin ameliorated dermal fibrosis. They decreased dermal thickness and tissue IL-17A and collagen 3A mRNA levels. Secukinumab and metformin exhibit anti-fibrotic effects in the BLM-induced dermal fibrosis.