EXPRESSION OF TRANSCRIPTS FOR GRA AND GRB ISOFORMS AND 11£]HSD1 AND 11£]HSD2 IN MONONUCLEAR CELLS FROM PERIPHERAL AND PLEURAL COMPARTMENTS OF PATIENTS WITH TB PLEURISY

D'ATTILIO, LUCIANO; DÍDOLI, GRISELDA; SANTUCCI, NATALIA; DÍAZ, ARIANA; MARCHESINI, MARCELA; BOGUE, CRISTINA; TRINI, ERNESTO; GIRI, ADRIANA; BOTTASSO, OSCAR; BAY, MARÍA LUISA

Lima

Congreso; X Congreso de la Asociación Latinoamericana de Inmunología ALAI 2012; 2012

Mycobacterium tuberculosis (Mtb) is a major pathogen for humans. Our previous studies in patients with pulmonary tuberculosis (TB) showed markedly decreased plasma levels of dehydroepiandrosterone (DHEA) together with augmented concentrations of cortisol and pro- and anti-inflammatory cytokines. Studies on the expression of glucocorticoid receptors isoforms (GRƒÑ and £] and enzymes regulating cortisol availability (11beta-hydroxysteroid dehydrogenase type 1; 11£]SD1 and type 2; 11£]SD2) in peripheral blood mononuclear cells (PBMC) indicated a lower mRNA GRƒÑ/ƒÒ ratio together with higher 11£]SD1 in cases with severe pulmonary TB suggesting certain degree of resistance to endogenous GC. Pleural TB (PLTB) is the most common manifestation of extrapulmonary TB being characterized by a rather effective immune response against Mtb. Supporting this view, our studies on the immuno-endocrine responses in patients with TB pleurisy revealed increased levels of IL-1ƒÒ, reduced cortisol concentrations, decreased cortisol/DHEA ratio in their pleural fluids (PFTB) together with a higher lymphoproliferative capacity regarding their peripheral compartment. Extending these findings we have now analyzed the expression of GRƒÑ and GR£]isoforms and 11£]SD1 and 11£]SD2 by real time PCR in PBMC y PFMC in patients with either PLTB (n=7) or non TB pleurisy (NoTBPL, n=6). Both study groups presented a significantly increased expression of 11£]SD1 and GRƒÑ in PFMC respect to PBMC (p<0.05) with no detectable amounts of mRNA for 11£]SD2. There were no between-group differences in the expression of GRƒÒ or GRƒÑ/ƒÒ ratio by compartments, although the expression of GRƒÑ and GRƒÒ was negatively correlated in PFMC from PLTB patients (r: -0.83; n=7, p<0.05). The pattern of molecular expression at the pleural space is compatible with a microenvironment favouring an optimization (a better performance) of immune-endocrine effects of cortisol