title: Adjunctive rapamycin and CsA treatment inhibits monocyte/macrophage associated cytokines/chemokines in sensitized cardiac graft recipients.
abstract: 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.affiliation: Harvard Medical School, Division of Immunology, Beth Israel-Deaconess Medical Center, Boston, MA, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Wasowska
authors.forename: X X
authors.initials: XX
authors.lastname: Zheng
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
authors.forename: J W
authors.initials: JW
authors.lastname: Kupieck-Weglinski
mesh_terms: 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
chemical_list: D018925:Chemokines; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine; D020123:Sirolimus