title: Profibrotic cytokines and lymphocyte proliferation in stable renal allograft recipients treated with or without cyclosporine A.
abstract: Profibrotic cytokines such as transforming growth factor-beta 1 (TGF-beta1) and endothelin-1 (ET-1) are involved in the pathogenesis of chronic allograft nephropathy. We assessed the effect of maintenance immunosuppression with or without cyclosporine A on TGF-beta1 and ET-1 expression as well as lymphocyte proliferation in renal allograft recipients. Patients were divided into groups according to their maintenance immunosuppression: A, azathioprine + methylprednisolone; B, cyclosporine A + azathioprine + methylprednisolone. TGF-beta1 and ET-1 plasma concentrations were not different between both groups. TGF-beta1 concentrations in cell culture supernatants and lymphocyte proliferation were higher in group B as compared to group A. No correlation was found between TGF-beta1 plasma concentrations and lymphocyte proliferation. Multiple linear regression analysis revealed that patient characteristics influence TGF-beta1 and ET-1 expression. In conclusion, plasma levels of profibrotic cytokines do not reflect the existing profibrotic potential of immunosuppressive drugs. Demographic factors and the employed co-medication confound the results.
authors.affiliation: Department of Internal Medicine-Nephrology, University Hospital Charité, Campus Mitte, Schumannstrasse 20/21, 10117 Berlin, Germany. johannes.waiser@charite.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Waiser
authors.forename: Michael
authors.initials: M
authors.lastname: Schneider
authors.forename: Sara
authors.initials: S
authors.lastname: Eljazyfer
authors.forename: Torsten
authors.initials: T
authors.lastname: Slowinski
authors.forename: Petra
authors.initials: P
authors.lastname: Glander
authors.forename: Gunilla
authors.initials: G
authors.lastname: Einecke
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Torsten
authors.initials: T
authors.lastname: Böhler
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001379:Azathioprine / Q000008:administration & dosage / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D003401:Creatine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D016903:Drug Monitoring; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016014:Linear Models; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D019332:Endothelin-1; D007166:Immunosuppressive Agents; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D001379:Azathioprine; D003401:Creatine; D008775:Methylprednisolone