Suppression of allograft responses induced by interleukin-6, which selectively modulates interferon-gamma but not interleukin-2 production.
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.
Tomura
M
M
Basic Research Laboratories, Toray Industries Inc., Kanagawa, Japan.
Nakatani
I
I
Murachi
M
M
Tai
X G
XG
Toyo-oka
K
K
Fujiwara
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D015850:Interleukin-6; D007371:Interferon-gamma