Altered Cortisol/DHEA Ratio in Tuberculosis Patients and its Relationship with Abnormalities in the Mycobacterial‐driven Cytokine Production by Peripheral Blood Mononuclear Cells

Abstract

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‐γ) 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‐γ 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‐γ values. An inverse correlation was found between the cortisol/DHEA ratio and IFN‐γ levels. Novel evidence is provided showing that the balance between cortisol and DHEA is partly responsible for the immune perturbations seen in TB patients.

Adrenal Steroids Modulate the Immune Response during Brucella abortus Infection by a Mechanism That Depends on the Regulation of Cytokine Production

“…The effects of DHEA are often opposed by the other important adrenal steroid, cortisol (18). The cortisol/DHEA ratio is abnormal under various pathological conditions such as AIDS, rheumatoid arthritis, and tuberculosis (18)(19)(20). In previous studies, significantly higher levels of cortisol in serum were reported in patients with acute brucellosis than in brucellosis patients at the end of antibiotic treatment or than in healthy subjects (21).…”

“…Macrophages/monocytes were recognized to play an important role in resistance to facultative intracellular bacteria such as Brucella, and activation of macrophages by specifically committed T lymphocytes formed the basis for cell-mediated immunity. However, B. abortus is endowed with a panoply of survival stratagems to evade immune responses and survive inside macrophages, creating a safe niche of replication inside the host (10-13).Several cytokines that are produced during B. abortus infec- [18][19][20]. In previous studies, significantly higher levels of cortisol in serum were reported in patients with acute brucellosis than in brucellosis patients at the end of antibiotic treatment or than in healthy subjects (21).…”

“…Several cytokines that are produced during B. abortus infec- [18][19][20]. In previous studies, significantly higher levels of cortisol in serum were reported in patients with acute brucellosis than in brucellosis patients at the end of antibiotic treatment or than in healthy subjects (21).…”

A high corticosterone/DHEA-s ratio in young rats infected with Trypanosoma cruzi is associated with increased susceptibility

“…The results of the present study suggest that the high CT/DHEA-s ratio (Fig. 4B) could exert a negative influence on the protective response, which has been observed in other chronic infections, such as tuberculosis (Bozza et al 2007) and human immunodehuman immunodeficiency virus (HIV) (Christeff et al 1999). In schistosomiasis, the immunosuppressive effects of hydrocortisone and dexamethasone are counteracted by DHEA, which suggests that there is a tightly controlled balance in the secretion of these hormones that regulates the inflammatory response (Morales-Montor & Hall 2007).…”

Effect of smoking on acute phase reactants, stress hormone responses and vitamin C in pulmonary tuberculosis

“…This contention is supported by several recent studies describing the selective anti-mycobacterial actions of vitamin C, either bactericidal or bacteriostatic, depending on the concentration of the vitamin and availability of iron [10][11][12] . In addition, vitamin C which is stored in the adrenal gland, is also required for synthesis of catecholamines 13 , a component of the endogenous anti-inflammatory stress hormone response, which may ameliorate pulmonary damage and dysfunction in TB [14][15][16] . However, the possible relationships between cigarette smoking, vitamin C status, and the acute phase and stress hormone responses in patients with pulmonary TB have not been well characterised.…”