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

Takuya Nishina, Yoshio Naomoto, Akira Gouchi, Mehmet Gunduz, Yasuhiro Shirakawa, Tetsuji Nobuhisa, Takayuki Motoki, Satoshi Kusaka, Minoru Haisa, Junji Matsuoka, Eiichi Nakayama, Noriaki Tanaka

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Abstract

Background. Despite the availability of a variety of immunosuppressive agents, acute rejection and infection after organ transplantation remain serious problems. Methods and Results. 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. Conclusions. 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.

Original languageEnglish
Pages (from-to)456-459
Number of pages4
JournalTransplantation
Volume77
Issue number3
DOIs
Publication statusPublished - Feb 15 2004

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ASJC Scopus subject areas

  • Transplantation

Cite this

Nishina, T., Naomoto, Y., Gouchi, A., Gunduz, M., Shirakawa, Y., Nobuhisa, T., Motoki, T., Kusaka, S., Haisa, M., Matsuoka, J., Nakayama, E., & Tanaka, N. (2004). Macrophage colony-stimulating factor inhibits tumor necrosis factor production and prolongs skin graft survival. Transplantation, 77(3), 456-459. https://doi.org/10.1097/01.TP.0000100483.41935.B5