| First Author | Tomura M | Year | 1997 |
| Journal | Transplantation | Volume | 64 |
| Issue | 5 | Pages | 757-63 |
| PubMed ID | 9311716 | Mgi Jnum | J:43100 |
| Mgi Id | MGI:1097068 | Doi | 10.1097/00007890-199709150-00017 |
| Citation | Tomura M, et al. (1997) Suppression of allograft responses induced by interleukin-6, which selectively modulates interferon-gamma but not interleukin-2 production. Transplantation 64(5):757-63 |
| abstractText | 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. |
