Expression levels of mRNA for GRa, GRB, 11BHSD1 and GRa/B ratio in peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis, throughout the 6-month course of etiological treatment and 3 month following its completion.

DATTILIO L; DIAZ A; BONGIOVANNI B; SANTUCCI N; DIDOLI G; GARDEÑEZ W; DEL REY A; BESEDOVSKY H; BOTTASSO O; BAY ML

Mil´qn

Congreso; 15th International Congress of Immunology, Milán 22-27 Agosto 2013; 2013

IUIS

Patients with pulmonary tuberculosis (TB) show several immune-endocrine alterations, like decreased plasma levels of dehydroepiandrosterone together with augmented concentrations of proinflammatory cytokines and cortisol. The latter continues to be increased throughout treatment, whereas IL-6 and IFN-g fall to control values and DHEA concentrations normalize. Studies on the expression of mRNA for glucocorticoid receptors isoforms (GRa and B) and enzymes regulating cortisol availability (11beta-hydroxysteroid dehydrogenase type 1; 11BHSD1 and type 2; 11BHSD2) PBMC indicate a lower GRa/B ratio and higher 11BHSD1 in severe pulmonary TB. Extending this analysis we now analyzed the expression of mRNA for GRa, GRB, 11BHSD1 and GRa/B ratio in PBMC from and 16 TB -HIV negative- patients, bled at diagnosis (T0), two (T2), four (T4) and 6 months (T6) of treatment as well as 3 months later (T9) and 19 age- and sex-matched healthy controls, for comparison purposes. Transcript levels for GRa at T0 remained within controls values, rose significantly throughout treatment (p<0.05) decreasing to normal levels by T9. Conversely, the GRβ expression, that was augmented at diagnosis (p<0.03), decreased significantly in the remaining time-point evaluations (p<0.02). This resulted in a significantly reduced GRa/B ratio at T0 (p<0.03), reaching normal values from T2 thereafter (p<0.02). Expression of 11BHSD1 was augmented at T0 (p<0.05), but  further evaluations during and after specific treatment showed levels within the normal range (p<0.02). Clinical improvement and decreased inflammation resulting from specific treatment coexist with a milieu more suitable for the immunomodulatory effects of endogenous GC.