Evidence that production of interleukin 6 within the rejecting allograft coincides with cytotoxic T lymphocyte development.
Current evidence suggests that the development of allosensitized cytotoxic T lymphocytes within sponge matrix allografts takes place primarily in situ and may be regulated by the secretory products of the cells infiltrating the graft. In vitro studies have implicated IL-2, IL-4, and IL-6 in CTL development. We have reported that TNF-alpha, macrophage colony-stimulating factor, IL-1, IFN-alpha, and IFN-beta are present in the allograft, but that IL-2 and IL-4 cannot be detected at any time using specific bioassays. In this study, we found significantly higher levels of IL-6 within the allografts compared with the syngeneic grafts. Peak IL-6 activity coincided with the appearance of allosensitized CTL in the allografts. IL-6 concentration in the serum of sponge allografted mice was less than 1% of that found in the graft. The sponge fluid exhibited both hybridoma growth factor and hepatocyte-stimulating factor activities in vitro, and both these activities were neutralized by antibody to murine IL-6 but not by antibody to murine IL-1-beta or TNF-alpha. Messenger RNA for murine IL-6 was detected in the graft-infiltrating cells. The high level of IL-6 found in the allograft coincident with the appearance of cellular immunity suggests that this cytokine might play some role in the development of allospecific CTL in vivo.
Ford
H R
HR
Department of Surgery, University of Pittsburgh, Pennsylvania.
Hoffman
R A
RA
Tweardy
D J
DJ
Kispert
P
P
Wang
S
S
Simmons
R L
RL
D000818:Animals; D000906:Antibodies; D005260:Female; D006084:Graft Rejection; D007111:Immunity, Cellular; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology*
D000906:Antibodies; D015850:Interleukin-6; D012333:RNA, Messenger