GLUCOCORTICOID-RESISTANCE IN PERIPHERAL-BLOOD LYMPHOCYTES DOES NOT CORRELATE WITH NUMBER OR AFFINITY OF GLUCOCORTICOID-RECEPTORS IN CHRONIC-RENAL-FAILURE PATIENTS

Glucocorticoid (GC) resistance in patients with chronic renal failure (CRF) seriously impairs successive GC therapy after renal transplantat ion. We examined the relationship between GC-receptor (GC-R) parameter s in peripheral-blood mononuclear cells (PBMC) and PBMC resistance to GC in 21 CRF patients and 18 healthy subjects. Each subject group was divided into two subgroups according to PBMC sensitivity to prednisolo ne in a mitogen assay procedure; i.e., sensitive (IC50 < 381 ng/mL) an d resistant (IC50 > 381 ng/mL) groups. In healthy subjects, the mean G C-R B-max and Kd in quiescent PBMC of the GC-sensitive group were 2.89 +/- 1.23 fmol/10(6) cells and 4.00 +/- 2.24 nM, respectively, The B-m ax in these subjects significantly increased to 6.61 +/- 2.02 (257.7 /- 107.8%) after 24 h stimulation with concanavalin A (p < 0.01), whil e the Kd change was not significant. The GC-R B-max and Kd in quiescen t PBMC of the GC-resistant group were 5.33 +/- 1.37 fmol/10(6) cells a nd 3.20 +/- 1.39 nM, respectively. Both of these parameters, however, did not change significantly after mitogen stimulation. There was a si gnificant negative correlation between IC(50)s of prednisolone and inc rease-ratios (post/pre ratio) of B-max after mitogen stimulation (p < 0.05), In CRF patients, B-max and Kd in quiescent PBMC of the GC-sensi tive group were 6.04 +/- 2.35 fmol/10(6) cells and 3.49 +/- 1.72 nM, r espectively, while those in PBMC of the GC-resistant group were 5.13 /- 2.31 fmol/10(6) cells and 1.04 +/- 1.62 nM, respectively. The B-max and Kd were not significantly changed after mitogen stimulation in bo th subgroups of CRF. Moreover, in contrast to healthy subjects, there was no correlation between IC50 and GC-R parameters in CRF. We conclud ed that, in healthy subjects, decreased PBMC capacity to amplify GC-R numbers in response to mitogen is correlated with GC resistance, where as in CRF patients the resistant mechanism is not correlated with GC-R parameters. An unknown event might be involved in GC-resistance of CR F.