Differential suppression of dialysis patients' lymphocyte IFN-γ production by glucocorticoids and cyclosporine

William A. Briggs, Zu Hua Gao, Jing Jing Xing, Paul J. Scheel, Luis F. Gimenez, Michael J. Choi, James F. Burdick

Research output: Contribution to journalArticlepeer-review

Abstract

IFN-γ is a potent pro-inflammatory cytokine involved in the immunologic rejection of transplanted organs. Having previously demonstrated differential suppressive effects of methylprednisolone (MP), prednisolone (P) and cyclosporine (CsA) on dialysis patients' lymphocyte proliferative responses to phytohaemagglutinin (PHA), we studied the effects of these drugs on dialysis patients' lymphocyte IFN-γ production during mitogenic and allogeneic (MLR) stimulation. The mean ± SEM 50% inhibitory concentration (ng/ml) on cell proliferation was significantly lower for MP than P in PHA-stimulated haemodialysis (HD) patients' (35 ± 7 vs 152 ± 25, P < 0.001) and peritoneal dialysis (PD) patients' (35 ± 11 vs 134 ± 33, P = 0.001) cultures and in HD patients' MLR cultures (15 ± 3 vs 48 ± 9, P < 0.001). The mean ± SEM fractional responses (PHA or MLR ± drug/PHA or MLR) in culture supernatant IFN-γ concentrations were significantly lower with 10-7 M concentrations of MP than P in HD (0.19 ± 0.05 vs 0.31 ± 0.06, P = 0.01) and PD (0.30 ± 0.11 vs 0.46 ± 0.11, P < 0.05) PHA cultures and in HD MLR cultures (0.15 ± 0.04 vs 0.28 ± 0.07, P = 0.01), CsA (400 ng/ml) alone not only caused less than 50% inhibition of IFN-γ production in 15/27 HD PHA, 6/14 PD PHA and 4/13 HD MLR cultures, but actually stimulated it in 9 HD and 5 PD PHA cultures. The results suggest that: (1) MP has greater immunosuppressive potential than P for renal transplant recipients; (2) the stimulation of IFN-γ by CsA in some patients could be harmful in patients with initial allograft dysfunction; and (3) pre-transplant in-vitro assessment of recipients' PBMC responsiveness to glucocorticoids and CsA may help individualize the post-transplant immunosuppressive regimen.

Original languageEnglish (US)
Pages (from-to)804-808
Number of pages5
JournalCytokine
Volume8
Issue number10
DOIs
StatePublished - Oct 1996

Keywords

  • Cyclosporine
  • Dialysis patients
  • Glucocorticoids
  • IFN-γ

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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