Introduction: Glucocorticoids (GC) are routinely used in the treatment of patients with chronic inflammatory and autoimmune diseases due to their anti-inflammatory effects. However, long-term treatment with GCs is associated with severe side-effects limiting their therapeutic use. Moreover, responses of patients to GCs vary, ranging from increased sensitivity to low dose topically administered GC to inadequate response to high doses of GCs. Previously, our group has developed an in vitro GC-sensitivity assay assessing GC-mediated effects on glucocorticoid induced leucine zipper (GILZ) and interleukin-2 (IL-2) mRNA expression in peripheral blood mononuclear cells (PBMC). The aim of this ongoing research is to assess the suitability of the GC sensitivity assay to serve as an adjunct to clinical diagnosis of glucocorticoid sensitivity/resistance in patients with abnormal glucocorticoid response.

Methods: Three healthy controls and 4 patients with clinically suspected glucocorticoid hypersensitivity were assessed for dexamethasone-induced transactivation or transrepression of GILZ or IL-2 mRNA expression respectively in their PBMCs by RT-qPCR (quantitative polymerase chain reaction).

Results: Mean EC₅₀ (half effective concentration) of dexamethasone resulting in transactivation of GILZ were 11.3 nM (SD + 7.7) in patients and 7.7 nM (SD + 2.6) in healthy controls. Mean IC₅₀ (half inhibitory concentration) of dexamethasone resulting in transrepression of IL-2 were 24.3 nM (SD + 18.9) in patients and 17.4 nM (SD + 12.4) in healthy controls. Interestingly, one patient had an EC₅₀ for GILZ transactivation of 3.7 nM suggesting increased sensitivity to dexamethasone corresponding to the clinical findings.

Conclusion: The in vitro cellular bioassay using dexamethasone-induced transactivation/transrepression of GILZ/IL-2 gene expression shows potential applicability in assessing glucocorticoid receptor sensitivity in PBMCs of patients with clinically reported abnormal glucocorticoid response.