Nedocromil sodium ameliorates skin manifestations in a murine model of chronic graft-versus-host disease

Abstract

Dermal fibrosis, loss of cutaneous appendages, and loss of subcutaneous fat are the main manifestations of chronic graft-versus-host disease (cGVHD) in mice. Mast cells (MC) may have a role in cGVHD. To investigate this point we have evaluated the effect of a MC stabilizer (nedocromil sodium) and a MC activator (compound 48/80) on skin manifestations in a murine model of cGVHD (B10.D2 → BALB/c). Mice were treated with nedocromil sodium (5 mg/day) or compound 48/80 (10 μ g/day) from day −3 until day 15. Nedocromil ameliorated the skin features of cGVHD while compound 48/80 caused skin changes reminiscent of mild cGVHD in control mice. In addition nedocromil normalized peritoneal MC numbers and skin MC numbers and their activation state in the cGVHD mice. On the other hand compound 48/80 caused a complete disappearance of toluidine blue stainable peritoneal MC from cGVHD and control mice and decreased skin MC in controls. In summary, MC activation may play a negative role in the skin changes seen in cGVHD while MC stabilization ameliorates the skin manifestations of cGVHD and therefore may have a therapeutic benefit.