The immuno-endocrine component in the pathogenesis of tuberculosis

BOTTASSO O; BAY ML; BESEDOVSKY H; DEL REY A

SCANDINAVIAN JOURNAL OF IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2007 vol. 66 p. 166 - 175

0300-9475

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-c) 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-c 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 immunoendocrine interactions may affect the control of tissue damage and the development of protective immune responses, partly accounting for disease aggravation.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-c) 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-c 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 immunoendocrine interactions may affect the control of tissue damage and the development of protective immune responses, partly accounting for disease aggravation.