Immunoendocrine interactions: glucocorticoid receptor expression in pulmonary Tuberculosis of different severity

DATTILIO, L.; TRINI, E; BOZZA, V.; DÍDOLI, G.; NANNINI, LJ; GARDEÑEZ, W; GIRI ADRIANA ANGELICA; BOTTASSO, O. A.; BAY ML

Rio de Janeiro (Brasil)

Congreso; 13th International Congress of Immunology; 2007

International Society of Immunology

Glucocorticoids (GCs) exert their immunomodulatory effects by binding to the α isoform of the GC receptor (GR). Two isoforms of the GR are known to exist in humans: GRα and GRβ and their expression can be modulated by cytokines. GRβ fails to bind GCs and functions as a dominant negative inhibitor of GRα. Given this background, we have investigated whether the inflammatory response seen during pulmonary tuberculosis (TB) was associated with changes in the expression of GRα and GRβ. Fifteen patients with untreated TB [mild -M- (n=3), moderate -Mo- (n=7) and severe -Se- (n=5)] and 11 Controls, were analyzed for the expression of GRα and GRβ mRNA in peripheral blood mononuclear cells (quantitative RT-PCR, The Relative Standard Curve Method with SYBR Green I, internal control: Cyclophilin) and serum levels of IL-18, IFN-γ (ELISA, pg/ml), Cortisol (Cort) and Dehydroepiandrosterone-Sulfate (DHEA-S) (Electrochemoluminiscence nM). All TB patients had increased levels of IFN-γ and IL-18, the latter being statistically different from Controls (p<0.05). Compared to Controls, Mo and Se patients displayed higher Cort levels (p<0.03 and p<0.05, respectively), with DHEA-S concentrations being significantly reduced in all TB cases (p<0.04). While comparisons on GRβ expression revealed no between-group differences, Mo patients had an increased GRα expression [median and range, 81(67.8-168.7)] respect to controls [41.4(28.3-93.8), p<0.05]; this not being the case for Se patients [43.7(42.1-84.3)]. Taken together, our results suggest that patients with severe TB may present a relative resistance to GCs effects since augmented Cort levels were not accompanied by an increased expression of GR-α.