Effect of glucocorticoid therapy on glucocorticoid receptors in children with autoimmune diseases

Low-dose glucocorticoids (GC) achieve their action completely by classical genomic effects, mediated by the glucocorticoid receptor (GCR). In high dos es of GC, nongenomic effects have also been found, but it is still unclear to what extent they contribute to a beneficial outcome. In this study, we p resent a determination of the number of lymphocyte GCR sites and the bindin g affinity in healthy children and children with autoimmune diseases. We fu rther assess the effect of GC administration, especially of high-dose pulse therapy on the number of binding sites. The number of GCR sites per cell w as analyzed with [H-3]-dexamethasone radioligand binding assay and binding affinity (Kd given in nM) in peripheral blood mononuclear cells isolated fr om 48 healthy children and 35 patients. The patients were divided into thre e groups based on GC treatment: 0 mg/kg (group 1), 0.01-0.3 mg/kg orally (g roup 2), and 10-15 mg/kg i.v. pulse therapy (group 3) of prednisolone equiv alent per day. Gender- and age-independent normal values of 4338 +/- 1687 s ites/lymphocytes and Kd 6.7 +/- 2.2 nM were found. At 3463 +/- 1574, the nu mber of receptor sites in patients without GC (group 1) was significantly l ower than that of healthy volunteers (p < 0.05). In patients receiving GC t reatment, this value was reduced to 2952 +/- 512 (group 2). Significant dow n-regulation to a minimum of 479 +/- 168 (group 3) was found after pulse th erapy compared with untreated patients (p < 0.01). In pulse therapy, GC lea d to a fast and dramatic receptor down-regulation. We suppose that the incr ease in therapeutic success of pulse-therapy may partly be mediated through additional nongenomic effects.