Immunoendocrine Alterations during Human Tuberculosis as an Integrated View of Disease Pathology

Abstract

Tuberculosis (TB) is a chronic infectious disease accompanied by excessive and/or prolonged cytokine production, which might affect the immunoendocrine communication and favor the establishment of an adverse state with important alterations in essential biological functions. Studies in blood from TB patients showed increased levels of interferon γ (IFN-γ), interleukin 10 (IL-10), and IL-6, accompanied by a modest increase in the levels of cortisol, prolactin, and thyroid hormones and markedly augmented concentrations of growth hormone. Conversely, testosterone and dehydroepiandrosterone (DHEA) levels were profoundly decreased, resulting in an increased cortisol/DHEA ratio. The finding that culture supernatants from Mycobacterium-tuberculosis-stimulated peripheral blood mononuclear cells (PBMCs) of TB patients inhibit DHEA secretion by a human adrenal cell line indicates that immune cells from these patients can directly affect the synthesis of this hormone. Supporting the existence of bidirectional interactions, in vitro treatment of PBMCs from TB patients with physiological concentrations of cortisol inhibited mycobacterial antigen-driven lymphoproliferation and IFN-γ production, whereas DHEA suppressed transforming growth factor β production from cases with progressive disease. Further analysis showed that plasma DHEA levels correlated positively with the in vitroproduction of IFN-γ by mycobacterial-stimulated PBMCs, and the cortisol/DHEA ratio was inversely correlated with IFN-γ production. Lastly, it was also shown that the immunoendocrine imbalance in TB patients was associated with weight loss, which in turn correlated with the impairment on their specific in vitro cellular immune responses. These immunoendocrine interactions may play a detrimental role during TB, in terms of the development of protective immune responses, control of tissue damage and metabolic disorders, being implicated in disease aggravation and the ‘classic’ TB consumption.

Three Cases of Concurrent Infection with <i>Mycobacterium tuberculosis</i> and <i>Cryptococcus neoformans</i>

“…However, little is known about additional risk factors for the development of co-infection in patients without HIV infection. Tuberculosis infection causes alterations in cellular immunity and is recognized as a predisposing factor for developing cryptococcosis (4,23). Furthermore, cryptococcosis inhibits the production of TNF-α and predisposes patients to tuberculosis reactivation or infection (24,25).…”

IL-6 Mediates 11βHSD Type 2 to Effect Progression of the Mycobacterial Cord Factor Trehalose 6,6′-Dimycolate-Induced Granulomatous Response

“…The hypothalamic-pituitary-adrenal (HPA) axis is activated upon infectious assault, and more specifically, subsequently produced proinflammatory mediators [9,10] . There now appears to be a clear effect related to pathogenesis during mycobacterial infection [11][12][13] . HPA activation initiates release of biologically active glucocorticoids (GCs; cortisol in humans and corticosterone in rodents) into the bloodstream which function to dampen further inflammatory mediator production.…”

Mycobacterium bovis DNA Detection in Colostrum as a Potential Indicator of Vaccination Effectiveness against Bovine Tuberculosis

“…However, bacilli have pathogenic mechanisms to persist within M (23,24), triggering molecular signals in granulomas (25), which may exacerbate the inflammation and/or pathology during tuberculosis. The switch from a Th1 to a Th2 immune profile and tuberculosis progression have been associated with changes in hormonal profiles (26,27) similar to those present during pregnancy (28,29). Interaction between M. bovis and M results in a chronic inflammatory response to prevent mycobacterial growth but induces the development of granulomas, in which a balance of the immune response is needed to contain the infection.…”