Effectiveness of secukinumab and metformin treatments on bleomycin induced experimental scleroderma model

Although the pathogenesis of systemic sclerosis is not exactly known, it is thought that immune activation has prominent roles in pathogenesis. Secukinumab is monoclonal antibody againist interleukine (IL)-17A. Metformin is a widely used anti-diabetic medication. Recently, the pleiotropic effects of metformin have been disclosed, in particular its anti-proliferative, immunomodulating, and anti-fibrotic activities. The purpose of our study is to determine the prophylactic and therapeutic efficacy of secukinumab and metformin on bleomycin (BLM) induced skin fibrosis. 50 Balb/c female mice which their average age is 6 weeks and their average weight is 20-25 grams where selected. The 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 μl phosphate buffered saline (PBS), while the mice in other groups received 100 μl (100 μg) 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/week sc, and mice in the groups 4 and 5 received oral metformin (50 mg/kg/day) for 28 days. All groups of mice were sacrificed at the end of 4th week and tissue samples were taken for analysis. In addition to histopathological analysis, skin tissue mRNA expressions of IL-17 collagen 3A were measured by real-time PCR. Repeated BLM injections had caused dermal fibrosis. In addition, 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 IL-17A and collagen 3A mRNA levels. In conclusion, secukinumab and metformin may exhibit anti-fibrotic effects in the BLM induced skin fibrosis. Keywords: Experimental scleroderma, secukinumab, metformin.