BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
Authors: Mar Naranjo-Gómez; Nuria Climent; Joan Cos; Harold Oliva; Margarita Bofill; José M Gatell; Teresa Gallart; Ricardo Pujol-Borrell; Francesc E Borràs Journal: Immunology Date: 2006-08-24 Impact factor: 7.397
Authors: Shinji Nakashima; T Rinda Soong; Karen Fox-Talbot; Zhiping Qian; Salma Rahimi; Barbara A Wasowska; Charles A Rohde; Sabrina Chen; Joe G N Garcia; William M Baldwin Journal: Am J Transplant Date: 2005-04 Impact factor: 8.086
Authors: Shaowei Li; Fumiko Takeuchi; Ji-an Wang; Christopher Fuller; Gustavo Pacheco-Rodriguez; Joel Moss; Thomas N Darling Journal: J Exp Med Date: 2005-08-29 Impact factor: 14.307