Department of Neurobiology and Anatomy
Drexel University College of Medicine
2900 W. Queen Lane, Room186
Tomura, M., Nakatani, I., Murachi, M., Tai, X., Toyo-oka, K., & Fujiwara, H. (1997). Suppression of allograft responses induced by interleukin-6, which selectively modulates interferon-gamma but not interleukin-2 production. Transplantation.
Tomura, M., I. Nakatani, M. Murachi, X. Tai, K. Toyo-oka, and H. Fujiwara. “Suppression of Allograft Responses Induced by Interleukin-6, Which Selectively Modulates Interferon-Gamma but Not Interleukin-2 Production.” Transplantation (1997).
Tomura, M., et al. “Suppression of Allograft Responses Induced by Interleukin-6, Which Selectively Modulates Interferon-Gamma but Not Interleukin-2 Production.” Transplantation, 1997.
BACKGROUND Interferon (IFN)-gamma produced by activated T cells represents an important effector cytokine in mediating an inflammatory response.
METHODS The present study investigated the modulation of allograft responses by inhibiting IFN-gamma production. C57BL/6 (B6) lymph node cells were stimulated with class II H2-disparate B6-C-H-2bm12 (bm12) spleen cells.
RESULTS Addition of interleukin (IL)-6 to the primary B6 anti-bm12 mixed lymphocyte reaction (MLR) inhibited neither proliferative responses nor IL-2 production. However, IL-6 induced a dose-dependent suppression of IFN-gamma production in the same MLR cultures. B6 mice were engrafted with bm12 skin grafts, and IL-6 was given to bm12 skin graft recipients every other day. T cells from these recipient mice produced significantly less IFN-gamma in secondary B6 anti-bm12 MLR than those from bm12 skin graft recipients that had not received IL-6 injections. IFN-gamma production by these T cells was suppressed more strongly when the secondary MLR was conducted in the presence of IL-6. In addition to suppression of IFN-gamma expression, IL-6 injections resulted in prolongation of bm12 skin graft survival. The critical involvement of IFN-gamma in anti-bm12 rejection responses was substantiated by evidence that administration of anti-IFN-gamma monoclonal antibody strikingly prolonged bm12 skin graft survival. The prolongation of graft survival by in vivo treatment with either IL-6 or anti-IFN-gamma monoclonal antibody was found to be induced without blocking cellular infiltration of the grafts.
CONCLUSIONS These results indicate that IFN-gamma acts as a key cytokine in a B6 anti-bm12 allograft response and that IL-6 may down-regulate this response by inhibiting IFN-gamma production of alloreactive T cells.