The Adrenal Steroid Response during Tuberculosis and Its Effects on the Mycobacterial‐driven IFN‐γ Production of Patients and Their Household Contacts

Abstract

Earlier studies revealed that patients with tuberculosis (TB) have imbalanced immunoendocrine responses and that adrenal steroids [cortisol and dehydroepiandrosterone (DHEA)] can modify their specific cell-mediated immune response. Because most household contacts (HHCs) of contagious TB patients develop a subclinical and self-controlled process (latent TB), we studied some features of their immune and endocrine responses, particularly those related to the hypothalamic-pituitary-adrenal axis. Nineteen HHCs, 24 untreated TB patients (15 moderate, 9 advanced), and 18 healthy controls of similar age were studied. Patients had increased and reduced levels of cortisol and DHEA, respectively. DHEA levels were also reduced in HHCs. Stimulation of peripheral blood mononuclear cells (PBMC) with Mycobacterium tuberculosis sonicate resulted in increased in vitro lymphoproliferation in HHCs, while advanced patients showed the lowest response. Significantly higher amounts of interferon (IFN)-gamma were detected in supernatants from stimulated PBMC of HHCs when compared to controls and TB patients. Addition of cortisol to the cultures inhibited mycobacterial antigen-driven IFN-gamma production in all groups, although HHC supernatant contained significantly higher concentrations. In contrast, addition of DHEA to cultures of cells from HHCs resulted in increased IFN-gamma levels. These results suggest the existence of a particular immunoendocrine relation assuring a preserved IFN-gamma production in healthy housemates of TB patients.

A Multifaceted Analysis of Immune-Endocrine-Metabolic Alterations in Patients with Pulmonary Tuberculosis

“…In line with our former observations on the in vitro mycobacterial-driven immune responses [16], HHC and controls had easily noticeable in vitro responses to mycobacterial stimulation, whereas TB patients had an overall diminished lymphoproliferation and reduced 4-day IFN-γ, yielding statistically significant differences in both overall comparisons (Figure 2, panels A and C). Post hoc paired comparisons with the Bonferroni method revealed that HHC and controls had significantly higher lymphoproliferation and IFN-γ production than TB patients, with HHC also showing a significantly increased synthesis of this cytokine in relation to controls (Figure 2, panels A and C).…”

“…Nevertheless, a trend of HHC to display increased adipocytokines levels, together with lower amounts of DHEA and higher IL-6 concentrations (this mediator statistically significantly different from controls) was found. While meticulous clinical and radiological evaluation gave no indication of an overt disease, close contacts of TB patients are likely to course a subclinical TB infection [16], [51], and increased levels of IL-6 may reflect a subclinical inflammation.…”

A Clinical Correlate of the Dysregulated Immunoendocrine Response in Human Tuberculosis

“…Taken together with our studies showing that HHC mount a strong cell-mediated immune response to mycobacteria indicating a LTBI [9] , it can be assumed that controlled or progressive tuberculous infection coexist with two different types of immuno-endocrine relations. In fact, tuberculosis is accompanied by weight loss, decreased leptin and DHEA levels, and increased IL-18 concentrations, whereas no weight loss, normal to augmented leptin, unchanged IL-18 and decreased DHEA levels are seen in HHC.…”

“…Reduced DHEA levels in HHC may be also related to immune mechanisms triggered by LTBI, since we have previously shown that supernatants from cultures of antigen-specific stimulated mononuclear cells from TB patients inhibit DHEA production by adrenal cells [3] . Nevertheless, HHC can mount a strong cell-mediated immune response when stimulated with mycobacterial antigens [9] , suggesting the presence of a compensatory mechanism despite the diminished levels of DHEA.…”

Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies

“…Conversely, DHEA can directly and indirectly enhance Th1 T cell activity [ 21 ]. According to this, Mtb -specific IFN- γ secretion in TB patients correlated positively with DHEA plasma levels and inversely with cortisol/DHEA ratio [ 44 ].…”