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Titolo:
Glucocorticoid receptor mRNA in patients with ulcerative colitis: A study of responders and nonresponders to glucocorticoid steroid therapy
Autore:
Flood, L; Lofberg, R; Stierna, P; Wikstrom, AC;
Indirizzi:
Karolinska Inst, Huddinge Hosp, Dept Gastroenterol & Hepatol, SE-14186 Stockholm, Sweden Karolinska Inst Stockholm Sweden SE-14186 ol, SE-14186 Stockholm, Sweden Karolinska Inst, Huddinge Hosp, Dept Otorhinolaryngol, SE-14186 Stockholm,Sweden Karolinska Inst Stockholm Sweden SE-14186 gol, SE-14186 Stockholm,Sweden Karolinska Inst, Huddinge Hosp, Dept Med Nutr, SE-14186 Stockholm, Sweden Karolinska Inst Stockholm Sweden SE-14186 tr, SE-14186 Stockholm, Sweden Novum, Stockholm, Sweden Novum Stockholm SwedenNovum, Stockholm, Sweden
Titolo Testata:
INFLAMMATORY BOWEL DISEASES
fascicolo: 3, volume: 7, anno: 2001,
pagine: 202 - 209
SICI:
1078-0998(200108)7:3<202:GRMIPW>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
INFLAMMATORY BOWEL-DISEASE; BETA-ISOFORM; INTRAVENOUS TREATMENT; MONONUCLEAR-CELLS; EXPRESSION; DEXAMETHASONE; PREDNISOLONE;
Keywords:
adrenal insufficiency; glucocorticoid receptor; low-dose ACTH test; steroid resistance; ulcerative colitis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Flood, L Karolinska Inst, Huddinge Hosp, Dept Gastroenterol & Hepatol, SE-14186 Stockholm, Sweden Karolinska Inst Stockholm Sweden SE-14186 186 Stockholm, Sweden
Citazione:
L. Flood et al., "Glucocorticoid receptor mRNA in patients with ulcerative colitis: A study of responders and nonresponders to glucocorticoid steroid therapy", INFLAMM B D, 7(3), 2001, pp. 202-209

Abstract

Background and Aims: Up to 30% of patients with severe-to-moderate attacksof ulcerative colitis (UC) respond poorly to glucocorticosteroid (GCS) treatment. The reason for this unresponsiveness is unknown. Aim: Our aim was to evaluate possible differences in glucocorticoid receptor (GR) density in peripheral leukocytes and effects of low-dose GCS treatment on GR density and on the hypothalamic-pituitary-adrenal axis in UC patients who had received high-dose GCS treatment due to a moderate or severe attack. Eleven UC patients in remission who were responders (Rs) to previous GCS treatment werecompared with 10 patients who failed GCS therapy and had a colectomy (nonresponders, NRs). Ten healthy individuals served as controls. Methods: Quantitation of GR mRNA by a solution hybridization assay in peripheral leukocytes and a low-dose adrenocorticotropin hormone stimulation test was performed before and after low-dose dexamethasone (DEX) treatment for 14 days. The glucocorticoid-responsive gene for metallothionein Ha (MTIIa) was also analyzed by a solution hybridization assay in peripheral leukocytes. Results: Overall, basal GR mRNA levels were higher in patients than in controls (p < 0.0001). There were no significant differences between NRs and Rs. None of the groups down-regulated their GR mRNA levels in response to DEX treatment. Basal and stimulated cortisol levels decreased significantly only among NRs after DEX (p = 0.012 and 0.0093). MTIIa levels were lower in NRs as compared with Rs, both in mononuclear (p = 0.0059) and in polynuclear leukocytes (p = 0.030). Conclusion: Patients with UC in remission exhibit higher levels of GR mRNA in peripheral leukocytes. We speculate that this may be secondary to an underlying up-regulation of proinflammatory factors also present in patients in clinical remission. Differences in GR mRNA levels per se thus may not be important for the ability of patients with UC to respond to GCS treatment. The hypothalamic pituitary adrenal axis was suppressed by low-dose DEX treatment only in NRs, possibly indicating that steroid-resistance is not a generalized phenomenon. Lower levels of MTIIa in NRs may indicate a diminished efficiency of GR regulation in steroid-refractory patients.

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Documento generato il 18/01/20 alle ore 02:30:27