Evidence that changes in antimicrobial peptides during tuberculosis are related to disease severity, clinical presentation, specific therapy and levels of immune-endocrine mediators

Abstract

Given the role of host defense peptides (HDPs) in the defensive response against mycobacteria, we analyzed the circulating levels of LL-37, β-defensin-2 and -3 in newly diagnosed patients with pulmonary (PTB) or pleural tuberculosis (PLTB) in whom measurements of pleural fluids were also performed. Severe PTB patients displayed higher circulating amounts of β-defensin-3, statistically different from controls, further decreasing upon antimycobacterial treatment. LL-37 concentrations appeared within the normal range at diagnosis, but tended to increase during treatment, becoming statistically upon its completion in moderate cases. PLTB patients revealed decreased levels of β-defensin-2 in presence of increased amounts of β-defensin-3 and LL-37; in their plasma or pleural fluids. Considering the immune-endocrine dysregulation of tuberculosis, we also performed correlation analysis detecting positive associations between levels of cortisol, IL-6 and β-defensin-3 in plasma from untreated severe patients as did their dehydroepiandrosterone and LL-37 values. Increased presence of β-defensins, may represent an attempt to improve defensive mechanisms; which also take part in the inflammatory reaction accompanying TB, reinforced by the association with immune-endocrine mediators. The divergent profile of PLTB patients, decreased β-defensin-2 but increased β-defensin-3 and LL-37 levels, suggests a differential role of these HDPs in a situation characterized for its better protective response.