title: Cytokine mRNA expression in tolerant heart allografts after immunosuppression with cyclosporine, sirolimus or brequinar.
abstract: We sought to examine the impact of the preferential activation of Th2 cells on the induction and maintenance of a tolerant state in heart allograft rat recipients treated with a short course of cyclosporine (CsA), sirolimus (SRL) or brequinar (BQR). A quantitative polymerase chain reaction (PCR) method was used to measure the levels of cytokine mRNAs, namely interferon (IFN)-gamma and interleukin (IL)-2 in T helper 1 (Th1) cells and IL-4, IL-5 and IL-10 in Th2 cells. Our main findings were that on day 5 postgrafting allografts from untreated recipients had increased levels of IFN-gamma (216 +/- 119 fg), IL-2 (449 +/- 75 fg), IL-4 (6.2 +/- 1.3 fg), IL-5 (34.8 +/- 9.3 fg) and IL-10 (1554 +/- 184 fg) mRNAs compared with normal hearts. CsA reduced the levels of IFN-gamma, IL-2, IL-5 and IL-10, but not IL-4, mRNAs. SRL did not affect the expression of cytokine mRNAs. BQR decreased the levels of IFN-gamma, IL-2 and IL-10, but not IL-5 or IL-4 mRNAs. Compared with grafts from untreated recipients, those from CsA- or BQR-treated tolerant hosts (day 100) displayed undetectable IL-2 mRNA levels, and reduced levels of IFN-gamma, IL-4 and IL-10 mRNAs. In fact, the patterns of cytokine mRNA expression in grafts from CsA- and BQR-treated tolerant hosts were similar to those of normal hearts. Grafts from SRL-treated tolerant hosts merely showed slightly increased Th2 cell activity. In conclusion the selective activation of Th2 cells is not absolutely required for induction or maintenance of tolerance.
authors.affiliation: Department of Surgery, University of Texas Medical School at Houston, Texas 77030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tian
authors.forename: S M
authors.initials: SM
authors.lastname: Stepkowski
authors.forename: X
authors.initials: X
authors.lastname: Qu
authors.forename: M E
authors.initials: ME
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: B D
authors.initials: BD
authors.lastname: Kahan
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D000939:Epitopes; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D007519:Isoantigens / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D011090:Polyenes / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D020123:Sirolimus; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011798:Quinaldines
chemical_list: D001713:Biphenyl Compounds; D016572:Cyclosporine; D016207:Cytokines; D000939:Epitopes; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D007378:Interleukins; D007519:Isoantigens; D011090:Polyenes; D012333:RNA, Messenger; D020123:Sirolimus; C046943:brequinar; D011798:Quinaldines