Unique Identifier : AIDSLINE MED/99084427
BACKGROUND: The etiology of transplant arteriosclerosis is unknown, but
current data point to the alloimmune response. Previously, we found that
estradiol-17beta (E2) with immunosuppressant cyclosporine abolishes
major histocompatibility complex (MHC) class II expression in the
allograft. This study determines the effect of E2 on MHC class II
antigen expression in the allograft, in the absence of
immunosuppression. METHODS: Lewis male rats received orthotopic
abdominal aorta allografts from male Brown-Norway rats. The recipients
were treated continuously subcutaneously with either 20 microg x kg(-1)
x day1 of E2 (n=20) or placebo (n=20), from 2 days before
transplantation until death on posttransplant days 1, 3, 7, and 14. The
allografts were harvested and processed for morphometry and for
immunohistochemical staining of MHC class II antigens, macrophages, CD4
and CD8 T lymphocytes, interferon-gamma (IFN-gamma), and IFN-gamma
receptor. RESULTS: With E2 treatment, we observed that inducible MHC
class II antigen expression is abolished in the media of the vascular
allograft; the expression of IFN-gamma and IFN-gamma receptor is
unaffected; and macrophage infiltration of the vascular allograft is
inhibited significantly (P<0.01), whereas the CD4 and CD8 T lymphocytes
are not significantly (P=0.07) suppressed. The myointimal hyperplasia in
the allografts from E2-treated-recipients was 3-4-fold less than that
from the placebo-treated recipients. CONCLUSIONS: Without
immunosuppression, E2 inhibition of transplant arteriosclerosis