Suppression of allograft responses induced by interleukin-6, which selectively modulates interferon-gamma but not interleukin-2 production

Transplantation. 1997 Sep 15;64(5):757-63. doi: 10.1097/00007890-199709150-00017.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Dose-Response Relationship, Drug
  • Graft Survival / immunology
  • Histocompatibility Antigens Class II / pharmacology
  • Immune Tolerance / drug effects
  • Injections, Intraperitoneal
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-6 / pharmacology*
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Skin Transplantation / immunology
  • Skin Transplantation / pathology
  • Transplantation, Homologous / immunology*

Substances

  • Antibodies, Monoclonal
  • Histocompatibility Antigens Class II
  • Interleukin-2
  • Interleukin-6
  • Interferon-gamma