The role of vasopressin in the immunopathogenesis of experimental pulmonary tuberculosis.

Tuberculosis (TB) is a highly complex infectious disease caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb) characterized by chronic granulomatous inflammation of the lung. Immuneneuroendocrine interactions due to Mtb aggression and persistence have been associated with pathophysiology and disease outcome, and although poorly understood, neuroendocrine modulation could allow an improvement of conventional anti-TB chemotherapy. Vasopressin (Vp), a neurohypophyseal hormone with immunomodulatory effects, is abnormally high in some patients with pulmonary TB. In this study a BALB/c mice model of progressive pulmonary TB was used to determine whether vasopressin 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. Macrophages were the most important Vp localization. In order to study the Vp contribution to the pathogenesis of pulmonary TB, pharmacologic manipulation was done using an agonist and antagonist of Vp. Pharmacologic agonism of Vp receptors resulted in increased bacillary burdens and fibrosis, while blockade of Vp receptors reduced bacterial loads. Accordingly, treatment of infected alveolar macrophages with Vp in cell cultures, resulted in high number of intracellular Mtb and impaired cytokine production. Thus, it seems that Vp is ectopically produced in the tuberculous lungs, being macrophages its most important source; high and sustained production of Vp during active late disease has an anti-inflammatory and tissue reparative activities, which could be deleterious; further, its pharmacologic suppression reactivate protective immunity and contribute to shorten conventional chemotherapy, being a new possible form of immune-endocrine therapy. [ABSTRACT FROM AUTHOR]