Hormonal Disruption During Tuberculosis

BOTTASSO O

Dresden

Congreso; Congress of the International Society of Neuroimmunomodulation, October 20-22 2011, Dresden, Alemania; 2011

ISNIM

Tuberculosis (TB) accounts for an increasing morbidity and mortality across the world. One-third of the world population is infected with Mycobacterium tuberculosis and 5 to 10% of them are at risk of developing an active disease throughout the course of their lives. Typical manifestations comprise loss of weight and a variable degree of lung affectation. Our studies suggest that the chronic nature of the infection and the accompanying protracted immuno-inflammatory reactions are implied in a series of metabolic and neuroendocrine changes likely to affect systemic homeostasis and hence the host response. In fact, TB patients present an immune-endocrine imbalance characterized by increased circulating levels of IFN-gamma, IL-6, prolactin, thyroid hormones and cortisol in presence of decreased concentrations of testosterone and dehydroepiandrosterone (DHEA). Culture supernatants from M. tuberculosis-stimulated peripheral mononuclear cells (PBMC) of TB patients inhibited DHEA secretion by a human adrenal cell line, an effect partly reversed by TGF-beta neutralization. When treating PBMC of TB patients with physiological concentrations of both adrenal steroids, cortisol inhibited mycobacterial antigen-driven lymphoproliferation and IFN-gamma production, whereas DHEA suppressed TGF-beta production from cases with progressive disease. More recently, it was also shown that a series of immuno-endocrine compounds participating both in the regulation and/or redirectioning of energy sources and immune activity are related to the consumption state of TB patients, which in turn account for the impaired specific in vitro cellular immune responses they usually present. The cross-talk between the neuroendocrine and immune systems alters defensive mechanisms against the Mycobacterium and the ensuing disease outcome.