Glucocorticoid receptors, in vitro steroid sensitivity, and cytokine secretion in idiopathic nephrotic syndrome.

Abstract:

BACKGROUND:Glucocorticoids (GC) represent the mainstay of treatment of idiopathic nephrotic syndrome (INS) and might be involved in the pathogenesis of the disease. We evaluated basal secretion of cortisol, number and affinity of glucocorticoid receptors, dexamethasone (Dex)-mediated inhibition of concanavalin-A (Con-A)-stimulated peripheral blood mononuclear cell (PBMC) proliferation, and cytokine secretion in patients with INS. METHODS:Blood and saliva were obtained from 20 INS patients in relapse and 11 control patients. Cortisol concentrations were measured by radioimmunoassay. PBMC were isolated for binding and in vitro GC sensitivity assays. Cytokines were measured in supernatants of PBMC culture by enzyme-linked immunosorbent assay (ELISA). RESULTS:Salivary cortisol concentrations were similar in INS patients and control patients. Density and affinity of GC receptors were similar in steroid-sensitive (SS) patients and control, whereas in steroid-resistant (SR) patients they were variable. Lymphocyte proliferation after Con-A stimulation was inhibited by Dex in a dose-dependent manner in control and SS patients. Control and all clinically SS patients were steroid-sensitive by in vitro test, but control patients significantly presented more suppression of PBMC proliferation compared with SS patients. Basal- and Con-A-stimulated interleukin (IL)-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha levels were similar in control and INS patients, and all cytokines but IL-10 were significantly inhibited by Dex 10-6 mol/L. In SR patients, cytokine secretion remained elevated after treatment with high doses of Dex. CONCLUSION:Abnormalities of number and affinity of the GC receptor and altered secretion of cytokines may be involved in tissue sensitivity to GC in INS patients.

journal_name

Kidney Int

journal_title

Kidney international

authors

Carlotti AP,Franco PB,Elias LL,Facincani I,Costa EL,Foss N,Moreira AC,de Castro M

doi

10.1111/j.1523-1755.2004.00392.x

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

403-8

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)49722-4

journal_volume

65

pub_type

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