Immunoendocrine alterations during human tuberculosis as an integrated view of disease pathology.
Tuberculosis (TB) is a chronic infectious disease accompanied by excessive and/or prolonged cytokine production, which might affect the immunoendocrine communication and favor the establishment of an adverse state with important alterations in essential biological functions. Studies in blood from TB patients showed increased levels of interferon gamma (IFN-gamma), interleukin 10 (IL-10), and IL-6, accompanied by a modest increase in the levels of cortisol, prolactin, and thyroid hormones and markedly augmented concentrations of growth hormone. Conversely, testosterone and dehydroepiandrosterone (DHEA) levels were profoundly decreased, resulting in an increased cortisol/DHEA ratio. The finding that culture supernatants from Mycobacterium-tuberculosis-stimulated peripheral blood mononuclear cells (PBMCs) of TB patients inhibit DHEA secretion by a human adrenal cell line indicates that immune cells from these patients can directly affect the synthesis of this hormone. Supporting the existence of bidirectional interactions, in vitro treatment of PBMCs from TB patients with physiological concentrations of cortisol inhibited mycobacterial antigen-driven lymphoproliferation and IFN-gamma production, whereas DHEA suppressed transforming growth factor beta production from cases with progressive disease. Further analysis showed that plasma DHEA levels correlated positively with the in vitroproduction of IFN-gamma by mycobacterial-stimulated PBMCs, and the cortisol/DHEA ratio was inversely correlated with IFN-gamma production. Lastly, it was also shown that the immunoendocrine imbalance in TB patients was associated with weight loss, which in turn correlated with the impairment on their specific in vitro cellular immune responses. These immunoendocrine interactions may play a detrimental role during TB, in terms of the development of protective immune responses, control of tissue damage and metabolic disorders, being implicated in disease aggravation and the 'classic' TB consumption.
Bottasso
Oscar
O
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina. bottasso@uolsinectis.com.ar
Bay
María Luisa
ML
Besedovsky
Hugo
H
del Rey
Adriana
A
D000302:Adrenal Cortex / Q000166:cytology; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism; D006728:Hormones / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D007378:Interleukins / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015213:Neuroimmunomodulation; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000097:blood / Q000276:immunology / Q000503:physiopathology*
D017077:Culture Media, Conditioned; D006728:Hormones; D007378:Interleukins; D003687:Dehydroepiandrosterone; D007371:Interferon-gamma; D006854:Hydrocortisone