J. Goral et al., Reduced levels of hsp70 result in a therapeutic effect of 15-deoxyspergualin on acute graft-versus-host disease in (DAxLEW)F1 rats, IMMUNOBIOL, 202(3), 2000, pp. 254-267
We have shown previously that increased levels of hsp70, and antibodies rea
ctive with hsp70 parallel the onset and severity of graft-versus-host disea
se (GVHD) in a parent --> (DA x LEW)F1 rat model. In this study we have ass
essed the effect of reducing the levels of the 70 kDa heat shock protein (h
sp70), on the morbidity and mortality of acute GVHD in (DA x LEW)F1 rats. T
he reduction was accomplished by the administration of 15-deoxyspergualin (
DSG), an immunosuppressive agent which binds to a constitutively expressed
member of the 70 kDa heat shock protein Family. DSG administered via three
different protocols reduced GVHD-associated morbidity. One of the regimens,
which consisted of intermittent DSG administration, also significantly red
uced GVHD associated mortality. This DSG treatment reduced hsp70 levels in
spleen and lymph nodes, inhibited anti-hsp70 antibody production, and dimin
ished the serum levels of IL-2, IFN-gamma, TNF-alpha, and IL-10. IL-4 level
s sis in the serum did nor change during GVHD and were nor effected by DSG.
These results show chat the mechanism of DSG immunosuppressive effect in r
at GVHD may involve DSG's capacity to bind to hsp70, which in turn may lead
to a decrease In levels or circulating anti-hsp70 antibodies, and reduced
production of cytokines.