Macrophage colony-stimulating factor inhibits tumor necrosis factor production and prolongs skin graft survival.

Abstract

Despite the availability of a variety of immunosuppressive agents, acute rejection and infection after organ transplantation remain serious problems. We examined the effect of macrophage colony-stimulating factor (M-CSF) on the production of tumor necrosis factor (TNF) in a Bacille de Calmette Guérin-lipopolysaccharide-challenged mouse model. Both serial and repeated injections of M-CSF inhibited TNF production in a dose-dependent manner. Electrophoretic mobility shift assay showed that M-CSF-induced inhibition of TNF production was a result of suppression of nuclear factor-kappaB. High-dose M-CSF significantly prolonged skin graft survival in mice with orthotopic transplantation compared with the control and low-dose M-CSF groups. The combined administration of low-dose M-CSF and cyclosporine also significantly prolonged graft survival compared with the control and low-dose single agent-treated groups. Our results indicate that M-CSF at a high dose is a potent inhibitor of cytokine production and can potentially be used as an immunosuppressive agent for allograft rejection.