Interleukin-6 upregulates glucocorticoid receptor numbers in human osteoblast-like cells

Interactions between the endocrine and immune systems are well known with s pecial regard to the hypothalamic-pituitary-adrenal axis. Little of the lit erature focuses on the complex effects of cytokines on tissue responsivenes s to glucocorticoids (GC). In bone tissue, osteoblasts represent a valuable model for studying GC-cytokine interactions. Hence, we have studied two hu man osteosarcoma cell Lines (Saos-2 and MG-63) with different degrees of di fferentiation and different constitutive IL-6 production (3.4 +/- 0.3 (mean +/- SE) and 3309 +/- 578 pgi 10(6) cells). We measured glucocorticoid rece ptor (GR) number and affinity as a function of the exposure of cells to dif ferent amounts of IL-6. Incubation for 20 h with IL-6 at increasing concent rations up to 2000 pg/ml yielded a significant increase of GR binding sites in both cell lines. IL-6 was also able to reverse the inhibitory effect of dexamethasone (1 mu mol/l) on GR in both cell lines. In MG-63 cells, expre ssing higher concentrations of GR, IL-6 deprivation via a specific anti-IL- 6 antibody (100 ng/ml) significantly decreased GR. In Saos-2 cells, express ing lower concentrations of GR, a 40 h treatment with human IL-1 beta (10 n g/ml) significantly increased both IL-6 production and GR. This latter effe ct was completely abolished by co-treating the cells with the anti-IL-6 ant ibody. Our results provide evidence that IL-6 is an autocrine positive modu lator of GR number in human osteoblasts.