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The Immune-Endocrine-Metabolic Unit During Human Tuberculosis

[ Vol. 6 , Issue. 4 ]

Author(s):

Oscar Bottasso*, Maria Luisa Bay, Hugo Besedovsky and Adriana del Rey   Pages 314 - 322 ( 9 )

Abstract:


Tuberculosis (TB) accounts for an increasing morbidity and mortality across the world. Approximately 8.8 million new TB cases emerge and 1.6 million people die of this disease every year. Host defense against microbial pathogens involves an inflammatory reaction in which innate and adaptive immune mechanisms play an active role in its development. When the pathogen cannot be contained by the initial response, as usually occurs in TB, a systemic response characterized by multiple metabolic and neuroendocrine changes develops. Essential functions like defensive responses and metabolism are regulated by a series of molecules with pleiotropic effects, like pro-inflammatory cytokines, adrenal steroids, and adipocytokines; which affect both the regulation and/or redirectioning of energy sources and immune activity. Patients with TB, frequently displaying a consumption state, and their highly exposed close-household contacts (HHC) constitute “natural models” for analyzing this type of immune-endocrine-metabolic relation. We have shown the existence of an immune-endocrine imbalance in TB patients characterized by increased circulating levels of IFN-γ, IL-6, prolactin, thyroid hormones, cortisol, and growth hormone, accompanied by decreased concentrations of leptin and DHEA, and without significant differences in insulin-like growth factor-1. In contrast HHC coursing a latent subclinical infection, showed a modest decrease of DHEA in presence of increased amounts of leptin. In vitro studies showed that culture supernatants from M. tuberculosis-stimulated PBMC of TB patients inhibited DHEA secretion by a human adrenal cell line. It was also found that the unbalanced immune-endocrine relation of TB patients was associated to the weight loss they presented, which in turn accounted for the impairment on their specific in vitro cellular immune responses. The host response during TB results in an altered immune-endocrine communication, affecting essential biological functions, like the development of protective responses, control of tissue damage and metabolism, implied in a poorer disease course.

Keywords:

Tuberculosis, adaptive immunity, neuroendocrine regulation, metabolism, weight loss.

Affiliation:

Instituto de Inmunologia, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100, 2000, Rosario



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