Background. Although treatment of LEW rats with Rapamycin (RPM) prolongs th
e survival of LBNF1 cardiac allografts to ca, 50 days, it fails to prevent
late activation of macrophage/monocyte-associated chemokines.
Methods. A 7-day course with RPM or CsA was introduced at 1-week posttransp
lant in RPM pretreated hosts. At day 35, intragraft mRNA expression of IL-2
, IFN-gamma, TGF-beta, IL-12 (p40), MCP-1, and RANTES was evaluated,
Results. RPM as a sequential treatment markedly inhibited mRNA levels codin
g for IL-2/IFN-gamma, and MCP-1. However, RPM monotherapy failed to prevent
the expression of IL-12 (p40) and RANTES. Adjunctive treatment with CsA ma
rkedly depressed IL-12 (p40) and RANTES, and to a lesser extent MCP-1 mRNA,
as compared with RPM-treated groups. Significant increase of TGF-beta mRNA
expression was revealed after sequential RPM and adjunctive CsA treatment.
Conclusions. A combination of RPM and CsA is more effective in restraining
mRNA expression than RPM alone; however, either therapy is associated with
TGF P hyperexpression.