title: Impact of maintenance immunosuppressive regimens--balance between graft protective suppression of immune functions and a near physiological immune response.
abstract: The Symphony study showed superior 1-year kidney graft outcome in patients on immunosuppression with tacrolimus/mycophenolate mofetil (Tacr/MMF). To analyze whether differences in clinical outcome between maintenance regimens may be explained by their impact on clinically relevant immune parameters, we assessed CD4 helper activity, immunoglobulin-secreting cell (ISC) formation, neopterin, sCD30, and intracellular cytokine production in a prospective study in 77 renal transplant recipients treated with cyclosporine A/azathioprine (CsA/Aza), CsA/MMF, Tacr/Aza or Tacr/MMF at 2 years post-transplant. Tacr- compared with CsA-based immunosuppression was independently associated with increased IL-2 (P<0.0001, CD4 cells; P=0.014, CD8 cells) and CD4 cell IL-4 responses (P=0.046; stepwise logistic regression) resulting in physiological responses in Tacr/Aza patients as compared with 25 healthy controls. MMF versus Aza treatment was proven to be an independent variable associated with suppression of CD4 cell IL-10 responses (P=0.008), B-cell IL-6R expression (P<0.0001) and ISC formation [P=0.020, staphylococcus cowan strain I (SAC I); P=0.021, pokeweed mitogen (PWM)]. Our data suggest that Tacr/MMF had the most effective impact on graft protective Th2 responses (enhanced CD4 cell IL-4 by Tacr, decreased CD4 cell IL-10 responses by MMF) and suppression of B-cell functions (MMF), whereas Tacr/Aza was associated with physiological IL-2 and IL-4 and stronger humoral responses which may reduce the risk of infectious disease complications.
authors.affiliation: Department of Internal Medicine, University of Giessen, Klinikstrasse 36, Giessen, Germany. rolf.weimer@innere.med.uni-giessen.de
authors.forename: Rolf
authors.initials: R
authors.lastname: Weimer
authors.forename: Sabine
authors.initials: S
authors.lastname: Deisz
authors.forename: Hartmut
authors.initials: H
authors.lastname: Dietrich
authors.forename: Fabrice
authors.initials: F
authors.lastname: Renner
authors.forename: Rolf-Hasso
authors.initials: RH
authors.lastname: Bödeker
authors.forename: Volker
authors.initials: V
authors.lastname: Daniel
authors.forename: Shirin
authors.initials: S
authors.lastname: Kamali-Ernst
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ernst
authors.forename: Winfried
authors.initials: W
authors.lastname: Padberg
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus