The effect of sirolimus- or cyclosporine-based immunosuppression effects on T-cell subsets in vivo

C. Libetta, V. Sepe, M. Zucchi, V. Portalupi, F. Meloni, T. Rampino, A. Dal Canton

Research output: Contribution to journalArticlepeer-review

Abstract

While sirolimus (SRL) is thought to be a non-nephrotoxic agent, cyclosporine A (CsA) toxicity is a serious problem in kidney transplantation. We compared the effects of the two drugs on T-helper (Th) subsets in kidney transplant patients. We examined 24 first cadaver kidney recipients equally randomized to receive SRL/mycophenolate mofetil (MMF)/methylprednisolone (MP), or cyclosporine with either MMF or MP. The Th1 and Th2 subsets in peripheral blood were separated based on their production of interferon-γ (INFγ) or interleukin (IL)-4/IL-5. The lymphocytes were stimulated with phytohemoagglutinin or with allogenic CD3-depeted and irradiated antigen-presenting cells. Furthermore, the conversion potential of Th0 to Th1 was determined by measuring IL-12 and IL-18 levels after lipopolysaccharide challenge. When peripheral blood lymphocytes taken from SRL-treated patients were stimulated by phytohemoagglutinin, there were significantly lower INFγ-producing cells compared with the lymphocytes taken from patients treated with CsA. The number of IL-4/IL-5-producing cells did not differ among the patient groups. Release of IL-12 but not IL-18 from peripheral lymphocytes following treatment with lipopolysaccharide was significantly lower in the SRL-treated patients. These results show that compared with CsA, SRL caused a significant decrease in the Th1 lymphocyte subset associated with a significant reduction of IL-12 release.

Original languageEnglish
Pages (from-to)114-120
Number of pages7
JournalKidney International
Volume72
Issue number1
DOIs
Publication statusPublished - Jul 2007

Keywords

  • Cyclosporine A
  • Cytokines
  • Immunosuppression
  • Kidney transplantation
  • Sirolimus
  • T-helper

ASJC Scopus subject areas

  • Nephrology

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