Adjunctive rapamycin and CsA treatment inhibits monocyte/macrophage associated cytokines/chemokines in sensitized cardiac graft recipients.
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.
Wasowska
B A
BA
Harvard Medical School, Division of Immunology, Beth Israel-Deaconess Medical Center, Boston, MA, USA.
Zheng
X X
XX
Strom
T B
TB
Kupieck-Weglinski
J W
JW
D000818:Animals; D018925:Chemokines / Q000235:genetics*; D016572:Cyclosporine / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000627:therapeutic use*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D014185:Transplantation, Isogeneic
D018925:Chemokines; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine; D020123:Sirolimus