The neuro-endocrine-immune relationship in pulmonary and pleural tuberculosis: a better local profile in pleural fluid.

BACKGROUND: Tuberculosis (TB) is a major health problem worldwide. In TB, the immune and central nervous systems modulate each other. The two main components of this network are the hypothalamic-pituitary-adrenal axis (HPA) and autonomic nervous system (ANS). OBJECTIVE: To elucidate neuro-endocrine-immune (NEI) interactions in pulmonary (PTB) or pleural (PLTB) TB, we analysed the relationship among compounds from these systems. METHODS: We quantified levels of catecholamines, hormones and cytokines in plasma from patients with PTB (n = 46) or PLTB (n = 12) and controls (n = 32), and in the pleural fluid from PLTB patients. Transcript expression for genes involved in glucocorticoid-related function (quantitative real-time polymerase chain reaction) was also analysed in mononuclear cells (MCs) from peripheral blood (PBMC) or pleural effusion (PEMC) compartments. RESULTS: Both patient groups had increased plasma levels of pro- and anti-inflammatory cytokines, cortisol, growth hormone (GH) and dopamine, whereas insulin-like growth factor 1 (IGF-1) and dehydroepiandrosterone levels were decreased. The pleural fluid contained increased levels of pro-inflammatory cytokines, GH and IGF-1 and reduced levels of steroid hormones compared with their plasma counterparts. PBMCs from PTB patients had increased expression of transcripts for 11ß-hydroxysteroid dehydrogenase (11ßHSD1) and a decreased glucocorticoid receptor (GR) ratio (GRα/GRß). In PLTB cases, expression of 11ßHSD1 and GRα transcripts was higher in PEMCs. CONCLUSION: PTB patients seem to display adverse NEI dysregulation. Changes in pleural fluid are compatible with a more effective NEI reaction.

An adverse immune-endocrine profile in patients with tuberculosis and type 2 diabetes.

Diabetes is a risk factor for the development of pulmonary tuberculosis (TB) and both diseases present endocrine alterations likely to play a role in certain immuno-endocrine-metabolic associated disorders. Patients with TB, or with TB and type 2 diabetes (TB + T2DM) and healthy controls (HCo) were assessed for plasma levels of cortisol, dehydroepiandrosterone (DHEA), estradiol, testosterone, growth hormone (GH), prolactin, insulin-like growth factor-1 (IGF-1), cytokines (IL-6, IL-10, IFN-γ) and the specific lymphoproliferative capacity of peripheral blood mononuclear cells. All patients had higher levels of cortisol with a reduction in DHEA, thus resulting in an increased cortisol/DHEA ratio (Cort/DHEA). Increased prolactin and particularly GH levels were found in both groups of TB patients. This was not paralleled by increased concentrations of IGF, which remained within the levels of HCo. Estradiol levels were significantly augmented in patients TB, and significantly more in TB + T2DM, whereas testosterone levels were decreased in both groups of patients. IFN- γ and IL-6 concentrations were significantly increased in all TB, even further in TB + T2DM; while IL-10 was equally increased in both groups of TB patients. The in vitro specific proliferative capacity was decreased in both groups of patients as compared to that of HCo. The adverse immune-endocrine profile of TB seems to be slightly more pronounced in patients who also have T2DM.

Leptin does not enhance cell-mediated immune responses following mycobacterial antigen stimulation.

BACKGROUND: Tuberculosis (TB) is a infectious disease characterised by a profound immune-endocrine metabolic imbalance, including a diminution in leptin plasma levels. Leptin appears to be the link between nutritional status and the development of a protective immune response. OBJECTIVE: To examine the effects of leptin on the proliferation and production of interferon-gamma (IFN-γ) by peripheral blood mononuclear cells (PBMC) in TB patients and healthy controls stimulated with mycobacterial antigens with or without leptin. As macrophages are key cells in mycobacterial containment, the effect of leptin on the production of interleukin (IL) 1ß and IL-1Ra by the monocytic cell line THP-1 was also studied. RESULTS: Leptin diminished the proliferative capacity of PBMC on mycobacterial stimulation, and had no effect on IFN-γ production in terms of measurements in culture supernatants or intracytoplasmic analysis using flow cytometry. Real-time polymerase chain reaction studies of PBMC from TB patients revealed a preserved expression of leptin receptor. Furthermore, IL-1ß and IL-1Ra secretion by THP-1 cells was not modified by leptin treatment. CONCLUSION: The study results do not support the utility of treatment with leptin to correct immune imbalances due to TB.

Altered cortisol/DHEA ratio in tuberculosis patients and its relationship with abnormalities in the mycobacterial-driven cytokine production by peripheral blood mononuclear cells.

We have investigated the relationship between cortisol and dehydroepiandrosterone (DHEA) levels and the immune response to mycobacterial antigens in peripheral venous blood, from a male population of active tuberculosis patients and age-matched healthy controls of the same sex (HCo). Peripheral blood mononuclear cells were cultured for 36 or 96 h with whole sonicated Mycobacterium tuberculosis (WSA) for measurement of proliferation, interferon gamma (IFN-gamma) and interleukin-10 (IL-10) in culture supernatants. Comparisons on the in vitro mycobacterial-driven immune responses demonstrated that TB patients had a higher IL-10 production, a decreased lymphoproliferation and a trend to reduced IFN-gamma synthesis, in relation to HCo. Active disease was also characterized by increases in the plasma levels of glucocorticoids (GC) and reduced concentrations of DHEA which resulted in a higher cortisol/DHEA ratio respect the HCo group. Plasma DHEA levels were positively correlated with IFN-gamma values. An inverse correlation was found between the cortisol/DHEA ratio and IFN-gamma levels. Novel evidence is provided showing that the balance between cortisol and DHEA is partly responsible for the immune perturbations seen in TB patients.