Improvement of Sclerodermatous Graft-Versus-Host Disease in Mice by Niclosamide

Sclerodermatous graft-versus-host disease, a frequent complication of allogeneic hematopoietic stem cell graft, shares many features with systemic sclerosis, such as production of autoantibodies and fibrosis of skin and inner organs. Recent reports on the implication of signal transducer and activator of transcription 3 and of Wnt/β-catenin in fibrosis have prompted us to investigate the effects of the inhibition of both signaling pathways in a mouse model of sclerodermatous graft-versus-host disease, using niclosamide, an anthelmintic drug, with a well-defined safety profile. Sclerodermatous graft-versus-host disease was induced in BALB/c mice by B10.D2 bone marrow and spleen cell transplantation. Mice were treated every other day, 5 days a week, for 5 weeks by niclosamide. Clinical and biological features were studied 42 days after transplantation. Niclosamide reversed clinical symptoms including alopecia, vasculitis, and diarrhea and prevented fibrosis of the skin and visceral organs. Beneficial immunological effects were also observed: niclosamide decreased the production of effector memory CD4 and CD8 T cells, T-cell infiltration of the skin and visceral organs, and decreased productions of IL-4 and IL-13, and autoimmune B-cell activation. The improvement provided by niclosamide in the mouse model of sclerodermatous graft-versus-host disease provides a rationale for the evaluation of niclosamide in the management of patients affected by systemic fibrotic disease.