title: Effect of different immunosuppressive drugs on immune cells from young and old healthy persons.
abstract: BACKGROUND
  Life expectancy, as well as the average age of patients undergoing solid organ transplantation, increases constantly. Consequently, immunosuppressive therapy is no longer limited to young organ recipients.
  
  
  OBJECTIVE
  Here, we investigate how different types of immunosuppressive therapy, namely the calcineurin inhibitors cyclosporin A and tacrolimus, as well as the mTOR inhibitor rapamycin, affect the function of immune cells in young and elderly persons.
  
  
  METHODS
  Proliferation, cell viability, cytokine production (IL-2, IFN-γ), H2O2 production and telomere length of phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMCs) of young (n = 13; median age 27 years) and old (n = 19; median age 71 years) healthy donors were analyzed.
  
  
  RESULTS
  The inhibition of proliferation was dampened in PBMCs from elderly donors, especially after incubation with rapamycin. All three immunosuppressive drugs inhibited the production of IL-2 equally well, whereas the production of IFN-γ was less well inhibited by rapamycin. Both calcineurin inhibitors increased H2O2 concentrations after stimulation with PHA and led to a shortening of telomeres in PBMCs from young and old individuals. Rapamycin had only minor effects on H2O2 production and telomere length.
  
  
  CONCLUSIONS
  Our results demonstrate that the effects of immunosuppressive drugs on PBMCs differ between young and elderly persons. Calcineurin inhibitors compared to rapamycin have a more pronounced prosenescence effect. These data indicate that specific treatment regimens for the elderly might therefore be considered.
authors.affiliation: Immunology Division, Research Institute of Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Welzl
authors.forename: Georg
authors.initials: G
authors.lastname: Kern
authors.forename: Gert
authors.initials: G
authors.lastname: Mayer
authors.forename: Birgit
authors.initials: B
authors.lastname: Weinberger
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
authors.forename: Gisela
authors.initials: G
authors.lastname: Sturm
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
authors.forename: Christian
authors.initials: C
authors.lastname: Koppelstaetter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016559:Tacrolimus / Q000494:pharmacology; D059506:Telomere Shortening / Q000187:drug effects; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; C508594:IL2 protein, human; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010835:Phytohemagglutinins; D007371:Interferon-gamma; D016572:Cyclosporine; D006861:Hydrogen Peroxide; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D016559:Tacrolimus