Immuno-endocrine Component in the Pathogenesis of Tuberculosis

• Published in: Scandinavian journal of immunology 2007-08, Vol.66 (2-3), p.166-175
• Main Authors: Bottasso, O, Bay, M.L, Besedovsky, H, del Rey, A
• Format: Article
• Language: English
• Subjects: Animals; Cytokines - physiology; Cytokines - secretion; Humans; Mycobacterium tuberculosis; Neurosecretory Systems - immunology; Neurosecretory Systems - metabolism; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - metabolism; Tuberculosis, Pulmonary - microbiology; Tuberculosis, Pulmonary - pathology
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.1365-3083.2007.01962.x

Tuberculosis (TB) may be regarded as a disease in which the immune response to Mycobacterium tuberculosis, its etiologic agent, is engaged both in protection and pathology. Different T-lymphocyte subsets are involved in the immune response against M. tuberculosis, but production of interferon-gamma (IFN-γ) by T cells seems to be fundamental for disease control. Th1-type cytokine responses predominate in patients with mild or moderate forms of pulmonary TB, whereas the production of Th2-type cytokines prevails in the severe disease. Since the immune response fails to definitely eradicate the pathogen, a chronic infection is established, and it is likely that a broad range of regulatory mechanisms operate in this situation. Cytokines released during the course of an immune response activate the hypothalamus-pituitary-adrenal axis leading to the production of glucocorticoids and dehydroepiandrosterone (DHEA), with known immunomodulatory effects. TB patients exhibit increased concentrations of interleukin-6 and cortisol in plasma, reduced DHEA and testosterone levels, together with remarkably increased growth hormone concentrations that were not accompanied by an expected raise in insulin-like growth factor-1. Significant increases in estradiol, prolactin, and thyroid hormone concentrations were also detected in patients. Cortisol inhibits the mycobacterial antigen-driven proliferation and IFN-γ production, whereas DHEA suppresses transforming growth factor beta production by lymphoid cells from TB patients with advanced disease. Furthermore, supernatants from cultures of M. tuberculosis-stimulated mononuclear cells of TB patients inhibit DHEA secretion by a human adrenal cell line. This type of immuno-endocrine interactions may affect the control of tissue damage and the development of protective immune responses, partly accounting for disease aggravation.