ADJUNCTIVE RAPAMYCIN AND CsA TREATMENT INHIBITS MONOCYTE/MACROPHAGE ASSOCIATED CYTOKINES/CHEMOKINES IN SENSITIZED CARDIAC GRAFT RECIPIENTS1

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Abstract
Although treatment of LEW rats with Rapamycin (RPM) prolongs the survival of LBNF1 cardiac allografts to ca. 50 days, it fails to prevent late activation of macrophage/monocyte-associated chemokines. A 7-day course with RPM or CsA was introduced at 1-week posttransplant 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. RPM as a sequential treatment markedly inhibited mRNA levels coding 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 markedly 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. A combination of RPM and CsA is more effective in restraining mRNA expression than RPM alone; however, either therapy is associated with TGF-beta hyperexpression.