The neuro-endocrine-immune relationship in pulmonary and pleural tuberculosis: A better local profile in pleural fluid

Abstract

BACKGROUND: Tuberculosis (TB) is a major health problem worldwide. In TB, the immune and central nervous systems modulate each other. The two main components of this network are the hypothalamic-pituitary-adrenal axis (HPA) and autonomic nervous system (ANS). OBJECTIVE: To elucidate neuro-endocrine-immune (NEI) interactions in pulmonary (PTB) or pleural (PLTB) TB, we analysed the relationship among compounds from these systems. METHODS: We quantified levels of catecholamines, hormones and cytokines in plasma from patients with PTB (n = 46) or PLTB (n = 12) and controls (n = 32), and in the pleural fluid from PLTB patients. Transcript expression for genes involved in glucocorticoid-related function (quantitative real-time polymerase chain reaction) was also analysed in mononuclear cells (MCs) from peripheral blood (PBMC) or pleural effusion (PEMC) compartments. RESULTS: Both patient groups had increased plasma levels of pro- and anti-inflammatory cytokines, cortisol, growth hormone (GH) and dopamine, whereas insulin-like growth factor 1 (IGF-1) and dehydroepiandrosterone levels were decreased. The pleural fluid contained increased levels of pro-inflammatory cytokines, GH and IGF-1 and reduced levels of steroid hormones compared with their plasma counterparts. PBMCs from PTB patients had increased expression of transcripts for 11β-hydroxysteroid dehydrogenase (11βHSD1) and a decreased glucocorticoid receptor (GR) ratio (GRα/GRβ). In PLTB cases, expression of 11βHSD1 and GRα transcripts was higher in PEMCs. CONCLUSION: PTB patients seem to display adverse NEI dysregulation. Changes in pleural fluid are compatible with a more effective NEI reaction.