The clinical recovery of tuberculosis patients undergoing specific treatment is associated with changes in the immune and neuroendocrine responses

DÍAZ, ARIANA; BONGIOVANNI, BETTINA; DATTILIO, LUCIANO; SANTUCCI, NATALIA; DÍDOLI, GRISELDA; FERNÁNDEZ, ROCÍO DEL VALLE; KOVALEVSKI, LEANDRO; LIOI, SUSANA; GARDEÑEZ, WALTER; BRANDAN, NADIA; NANNINI, LUIS J; BESEDOVSKY, HUGO; DEL REY, ADRIANA; BOTTASSO, OSCAR; BAY, MARÍA LUISA

Pathogens and Disease

Oxford University Press

Lugar: Oxford; Año: 2017 vol. 75 p. 1 - 19

Tuberculosis (TB) caused by Mycobacterium tuberculosis is a health problem worldwide. Patients with pulmonary TB show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (DHEA) levels. Extending these findings, we now investigated the immune-endocrine profile of TB patients undergoing specific treatment. Patients (n=24) were bled at diagnosis (T0), 2, 4, 6 months after treatment initiation and 3 months following its completion. At T0 TB patients showed increased plasma levels of IL-6, C reactive protein, IFN-g and TGF-B. These mediators decreased during treatment, reaching levels similar to those from healthy controls (n=26). Specific treatment led to an increased lymphoproliferative response along with clinical improvement. Newly diagnosed patients had low levels of DHEA, with increased cortisol amounts and Cortisol/DHEA ratio, which normalized upon specific treatment. As regards glucocorticoid receptors (GR), TB patients at diagnosis presented a reduced mRNA GRαlpha/GRbeta ratio in their peripheral blood mononuclear cells. Further, multivariate analysis showed that Cortisol/DHEA ratio was positively associated with inflammatory mediators for which this ratio may constitute a disease biomarker. Anti-mycobacterial treatment results in a better immune-endocrine scenario for the control of physiopathological processes accompanying disease development and hence implied in clinical recovery.