Involvement of Vasopressin in the Pathogenesis of Pulmonary Tuberculosis: A New Therapeutic Target?

Abstract

Tuberculosis (TB) is a highly complex infectious disease caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb). It is characterized by chronic granulomatous inflammation of the lung and systemic immune–neuroendocrine responses that have been associated with pathophysiology and disease outcome. Vasopressin (VP), a neurohypophysial hormone with immunomodulatory effects, is abnormally high in plasma of some patients with pulmonary TB, and is apparently produced ectopically. In this study, a BALB/c mouse model of progressive pulmonary TB was used to determine whether VP may play a role in TB pathophysiology. Our results show that VP gene is expressed in the lung since early infection, increasing as the infection progressed, and localized mainly in macrophages, which are key cells in mycobacterial elimination. Pharmacologic manipulation using agonist and antagonist compounds showed that high and sustained stimulation of VPR resulted in increased bacillary burdens and fibrosis at lungs, while blockade of VP receptors reduced bacterial loads. Accordingly, treatment of infected alveolar macrophages with VP in cell cultures resulted in high numbers of intracellular Mtb and impaired cytokine production. Thus, we show that VP is ectopically produced in the tuberculous lungs, with macrophages being its most possible target cell. Further, it seems that chronic vasopressinergic stimulation during active late disease causes anti-inflammatory and tissue reparative effects, which could be deleterious while its pharmacologic suppression reactivates protective immunity and contributes to shorten conventional chemotherapy, which could be a new possible form of immune-endocrine therapy.

Profiling the immune response to Mycobacterium tuberculosis Beijing family infection: a perspective from the transcriptome

“…Subsequently, serial dilutions were made in the liquid culture medium Middlebrook 7H9 USA and were sown in 7H10 Middlebrook plates. The viability of intracellular bacteria was determined by counting colony forming units (CFUs) [ 14 ]. The cytokines TNF-α, IFN-γ, IL-12P70 and IL-10 present in the supernatant of infected cells and in the supernatant of non-infected macrophages were determined in a single measure using ELISA kits (BioLegend Company, CA, USA) according to manufacturer´s instructions.…”

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective

“…Chassin et al, illustrated that administration of AVP V2 receptor agonist deamino-8-D-AVP reduces inflammatory changes in patients with pyelonephritis due to inhibition release of chemokines and NF-κB pathway, suggesting immune-regulatory effect of AVP [23] . However, AVP antagonist in patients with pulmonary tuberculosis restores the activity of protective immunity to counterbalance high AVP level in late active phase of disease [24] . In addition, beyond procalcitonin and C-reactive protein (CRP), AVP might be a promising biomarker in the diagnosis and poor prognosis of pneumonia [25] .…”

ACE2 in the second act of COVID‐19 syndrome: Peptide dysregulation and possible correction with oestrogen

“…Ang III and dynorphin stimulate the secretion of vasopressin, which appears to be affected in severe COVID‐19 patients, in whom a pronounced euvolemic hyponatraemia has been observed 48,49 . Vasopressin has been recently identified as an immunomodulator that drives inflammatory responses in the lung by triggering macrophage activation and polarisation to a reparative phenotype, increasing lung fibrosis and reducing the effectiveness for pathogen clearance 50 …”

“…48,49 Vasopressin has been recently identified as an immunomodulator that drives inflammatory responses in the lung by triggering macrophage activation and polarisation to a reparative phenotype, increasing lung fibrosis and reducing the effectiveness for pathogen clearance. 50 Antigenic processing and adaptive immune response are also altered in SARS-CoV-2 infected individuals with poor clinical outcomes. 51 In particular, Ang II promotes dendritic cell maturation and proinflammatory cytokine synthesis.…”