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Differential glucocorticoid responsiveness of dialysis patients' lymphocytes
W A Briggs1, Z H Gao, P J Scheel
1Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Objectives:
To evaluate in vitro glucocorticoid responsiveness of phytohemagglutinin (PHA)-stimulated lymphocytes from peritoneal dialysis (PD) patients compared to hemodialysis (HD) patients.
Design:
Cross-sectional study of prevalent PD and HD patients and concurrent control subjects.
Setting:
Urban outpatient dialysis unit.
Patients:
20 HD, 14 PD, and 20 control subjects.
Measurements:
Using standard lymphocyte culture techniques, the concentration of prednisolone (P) and methylprednisolone (MP) required to cause 50% inhibition (IC50) of the proliferative response to phytohemagglutinin (PHA) was determined from dose-response curves.
Results:
There was considerable heterogeneity in the sensitivities of individual patients' PBMC to glucocorticoid inhibition, especially those of HD patients' cells to P. The mean +/- SD IC50 for MP was significantly (p < or = 0.001) lower than that for P in each cohort: PD 11 +/- 5 vs. 34 +/- 18 ng/mL; HD 22 +/- 14 vs. 89 +/- 43 ng/mL; control subjects 14 +/- 11 vs. 55 +/- 56 ng/mL. Interestingly, the IC50 for both P and MP was significantly higher in HD than in either PD or controls (ANOVA, P: F = 6.56, p = 0.003; MP: F = 3.77, p = 0.03), indicating decreased sensitivity of HD lymphocytes to both drugs. There were no significant differences in mean IC50 values for either P or MP between PD and controls. No correlations were found between IC50 for either P or MP and patient age, gender, duration of dialysis, serum creatinine, serum albumin, or parathyroid hormone level.
Conclusions:
In vitro glucocorticoid responsiveness of dialysis patients' lymphocytes appears to be influenced by dialysis modality, but the factor(s) involved remains to be determined. The greater sensitivity of PD lymphocytes to both P and MP might result in better immunosuppression and less severe rejection after renal transplantation. MP may be particularly advantageous following renal transplantation for any patient manifesting relative or absolute in vitro resistance to P.