Is adrenal cortex from TB patients a source of cytokines which contributes to get independence from the HPA axis?

BINI E; CEREZO CORTES I; MARQUINA CASTILLO B; MARQUEZ VELASCO R; SANTUCCI N; GAMBOA DOMINGUEZ A; BAY ML; BOTTASSO O; HERNANDEZ PANDO R

Cancún

Congreso; Congress of the Latinamerican association of Immunology; 2018

ALAI

Introduction: The chronic nature of tuberculosis (TB) and the protracted immunoinflammatory reactions are implied in a series of metabolic and immune-endocrine changes accompanying the disease. In humans, TB induces chronic stress and the activation of neuro-hormonal circuits such as the hypothalamous-pituitary-adrenal (HPA) axis or the adrenergic nervous system, which leads to increased glucocorticoids (GC) and cathecolamines levels. Nevertheless, increased GC levels cannot only be explained by the HPA axis activationsince that corticotropin-releasing hormone and adrenocorticotropin hormone levels remains low. This could suggest an independent pathway from de HPA axis for GC production.The activation of TLRs expressed in adrenal cortex cells can induce cytokines production in sepsis. This may be the pathway that regulates the synthesis of adrenal steroids in TB patients. In a previous work carried out in testis from TB patient necropsies, we explored how components from the hypothalamous-pituitary-gonadal axis and cytokines are involved in disease immunopathology. Here, we analyzed the adrenal cortex from these necropsies in the aim to determine the production of cortisol, DHEA and diverse cytokines by adrenal TB patient glands.Methods and Materials: Adrenals from 14necropsies of patients dying from TB andfivepatients dying from cardiovascular diseases (no TB) as controls were studied by immunohistochemistry to detect Cortisol, DHEA, IL1β, IL1β- Receptor, IL6, TNFα, TGFβ, IFNγ and IL10. PCR analysis was performed in order to determine the presence of correspondent mRNAs.Results: Adrenals necropsies from TB patients exhibited positive staining to cortisol and the studied cytokines, exhibiting IL6 and TNFα particularly strong immunostaining in the cortical cells from the reticular and fascicular zones. The expression of DHEA decreased in TB patients, in comparison, adrenals from control patients exhibited increased DHEA levels. Adrenals from controls revealed slight or negative immunostaining for cortisol and cytokines. These results were confirmed by PCR analysis.Conclusions: Cortisol and pro-inflammatory cytokines, are produced by cells fromadrenal TB patient glands. That could regulate the production of steroid hormones by passing the central control.The persistence of the inflammatory process observed in TB patients may be responsible of the generation of new regulatory mechanisms, independent from the HPA axis. Despite central mechanisms of HPA still remain functional; in the case of a severe infectious disease as TB, an intra-adrenal mechanism of control may play an important rol in the immune-endocrine regulation.