Hormones – Cytokines – Signalling

Kidney International (2004) 65, 403–408; doi:10.1111/j.1523-1755.2004.00392.x

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

ANA PAULA DE CARVALHO, PANZERI CARLOTTI, PAULO BENEDITO FRANCO, LUCILA LEICO ELIAS, INALDA FACINCANI, ELAINE LOURENÇO, CARDEAL COSTA, NORMA FOSS, AYRTON CUSTóDIO MOREIRA and MARGARET DE CASTRO

Department of Pediatrics and Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São, Brazil

Correspondence: Margaret de Castro, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Avenida dos Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brazil. E-mail:castrom@fmrp.usp.br

Received 15 May 2003; Revised 3 July 2003; Re-revised 25 August 2003; Accepted 8 September 2003.

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Abstract

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

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.

Keywords:

glucocorticoid receptor number and affinity, Th1/Th2 cytokines, in vitro steroid sensitivity, idiopathic nephrotic syndrome

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