mRNA expression of alpha and beta isoforms of glucocorticoid receptor in peripheral blood mononuclear cells of patients with tuberculosis and its relation with components of the immunoendocrine response

D'ATTILIO, LUCIANO,; TRINI ERNESTO,; BETTINA BONGIOVANNI; DÍDOLI GRISELDA,; GARDEÑEZ WALTER,; NANNINI LUIS,; GIRI ADRIANA A,; BOTTASSO OSCAR,; BAY MARÍA L,

BRAIN BEHAVIOR AND IMMUNITY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2011 vol. 25 p. 461 - 467

0889-1591

We have analyzed the expression of GR isoforms by real time RT-qPCR in PBMCs from 19 HCo and 28 TB patients (8 mild; 12 moderate; 8 severe), HIV(-) and similar sex and age distribution. mRNA hGRa/b ratios were found higher in TB patients respect to those in control groups. However, when analyzing for disease severity such overall trend was at the expense of mild and moderate patients; with severe cases showing a lower mRNA GRa/b ratio respect the other patient groups. This suggested some degree of resistance to endogenous glucocorticoids in patients with severe TB, since hGRaa dimer mediates the biological functions of GC, with the GRb isoform acting as an inhibitor of GC activity. Levels of IL-6, IL-18, IFN-g and Cortisol were significantly increased in severe and moderate cases, whereas DHEA values were found decreased in them (p<0.05 respect to Hco). Analysis on the relationship between plasma levels of these immuno-endocrine mediators with the mRNA expression of hGRa and hGRb showed that IL-6 was positively associated with hGRa in mild TB patients (p<0.01), whereas a positive correlation between IFN-g and hGRb was observed in severe cases (p<0.01). As regard to hormones, DHEA was positively associated with hGRa in moderate and severe cases (p<0.01). This group also showed a positive correlation between hGRa and Cortisol/DHEA ratios (p<0.05). Changes in  the systemic levels of cytokine and adrenal hormones are likely to affect GR expression in a differential fashion and according to the amount of pulmonary affectation.