The relationship between mRNA expression of alpha and beta isoforms of glucocorticoid receptors (GR) is modulated by components of the immunoendocrine response in peripheral blood mononuclear cells (PBMC) of patients with pulmonary tuberculosis (TB)

DATTILIO, LUCIANO; TRINI, E; GIRI ADRIANA A; BOTTASSO O; BAY ML

Viña del Mar (Chile)

Congreso; IX Latin American Congress of Immunology; 2009

Latin American Association of Immunology

&lt;!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-GB; mso-fareast-language:ES-AR;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --&gt; We showed that mRNA-GRa/GRb (qRT-PCR) in PBMC from mild and moderate patients was significantly increased respect to healthy controls (HCo), without changes in severe TB. This suggested some degree of resistance to endogenous glucocorticoids in severe group. TB is accompanied by increased cortisol and pro-inflammatory cytokine concentrations and reduced dehydroepiandrosterone (DHEA) linked to disease severity. We investigated the relationship between plasma levels of immuno-endocrine mediators (TNF-a, IL-6, IL-18, IFN-g, Cortisol, DHEA, DHEAS; ELISA) with mRNA-GRa and mRNA-GRb in 19 HCo and 28 TB patients (8-mild;12-moderate;8-severe), HIV(-). Levels of IL-6, IL-18, IFN-g and Cortisol were increased in severe and moderate, whereas DHEA was decreased in them (p<0.05 vs Hco). IL-6 was positively associated with mRNA-GRa in mild TB (p<0.01), whereas a positive correlation between IFN-g and mRNA-GRb was observed in severe cases (p<0.01). DHEA was positively associated with mRNA-GRa in modetate and severe cases (p<0.01), and also with mRNA-GRb in severe (p<0.05). This group also showed a positive correlation between mRNA-GRa and Cortisol/DHEA ratio (p<0.05). Low DHEA concentrations may influence the active form of GR. 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.