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Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

Quiroga MF, Angerami MT, Santucci N, Ameri D, Francos JL, Wallach J, Sued O, Cahn P, Salomón H, Bottasso O - PLoS ONE (2012)

Bottom Line: DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals.HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals.We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, National Reference Center for AIDS, University of Buenos Aires School of Medicine, Buenos Aires, Argentina. fquiroga@fmed.uba.ar

ABSTRACT
Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

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Cortisol, dehidroepindrosterone-sulfate (DHEA-s), DHEA levels and Cortisol/DHEA ratio in HIV, HIV-TB, IRIS, HIV-LTB and HD.A. DHEA, B. DHEA-s, C. Cortisol and D. Cortisol/DHEA (ratio) levels in plasma of HIV+, HIV-TB, IRIS, HIV-LTB, and HD individuals. Bars indicate the mean ± SEM for each group. Horizontal lines indicate comparisons between groups and statistically significant differences. DHEA was measured by radioimmunoassay, DHEA-s by immunochemoluminiscence tests and Cortisol by electrochemiluminescence. HIV+ individuals n = 10, HIV-TB n = 21, IRIS n = 6, HIV-LTB n = 5, and HD n = 16. *: p < 0.05; **: p < 0.01; ***: p < 0.001.
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pone-0033061-g001: Cortisol, dehidroepindrosterone-sulfate (DHEA-s), DHEA levels and Cortisol/DHEA ratio in HIV, HIV-TB, IRIS, HIV-LTB and HD.A. DHEA, B. DHEA-s, C. Cortisol and D. Cortisol/DHEA (ratio) levels in plasma of HIV+, HIV-TB, IRIS, HIV-LTB, and HD individuals. Bars indicate the mean ± SEM for each group. Horizontal lines indicate comparisons between groups and statistically significant differences. DHEA was measured by radioimmunoassay, DHEA-s by immunochemoluminiscence tests and Cortisol by electrochemiluminescence. HIV+ individuals n = 10, HIV-TB n = 21, IRIS n = 6, HIV-LTB n = 5, and HD n = 16. *: p < 0.05; **: p < 0.01; ***: p < 0.001.

Mentions: In order to determine an association of DHEA, DHEA-s and cortisol levels with HIV-TB, IRIS, HIV+ or HIV-LTB conditions, we initially assessed adrenal hormone levels in plasma from patients and healthy donors (HD). Previously, we observed a profound decrease in DHEA levels in TB patients, in parallel to an increase in cortisol [25], We observed that DHEA plasma levels were significantly diminished in HIV-TB and IRIS patients compared to HD, HIV-LTB and HIV+ individuals (p<0.05), whereas DHEA-s levels were markedly diminished in HIV-TB with IRIS individuals (p<0.01 compared to HD, Fig. 1A y 1B). Furthermore, cortisol values were similar among groups except for HIV+ persons, whose cortisol levels were significantly lower compared to HIV-TB patients (p<0.05, Fig. 1C). When analyzing the cortisol/DHEA ratio, co-infected patients and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals (p<0.001, p<0.05, p<0.05 respectively, Fig. 1D), with HIV+ and HIV-LTB patients displaying slightly but still statistically significant lower cortisol/DHEA ratio than HD (p<0.01 and p<0.05 respectively, Fig. 1D).


Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

Quiroga MF, Angerami MT, Santucci N, Ameri D, Francos JL, Wallach J, Sued O, Cahn P, Salomón H, Bottasso O - PLoS ONE (2012)

Cortisol, dehidroepindrosterone-sulfate (DHEA-s), DHEA levels and Cortisol/DHEA ratio in HIV, HIV-TB, IRIS, HIV-LTB and HD.A. DHEA, B. DHEA-s, C. Cortisol and D. Cortisol/DHEA (ratio) levels in plasma of HIV+, HIV-TB, IRIS, HIV-LTB, and HD individuals. Bars indicate the mean ± SEM for each group. Horizontal lines indicate comparisons between groups and statistically significant differences. DHEA was measured by radioimmunoassay, DHEA-s by immunochemoluminiscence tests and Cortisol by electrochemiluminescence. HIV+ individuals n = 10, HIV-TB n = 21, IRIS n = 6, HIV-LTB n = 5, and HD n = 16. *: p < 0.05; **: p < 0.01; ***: p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3303789&req=5

pone-0033061-g001: Cortisol, dehidroepindrosterone-sulfate (DHEA-s), DHEA levels and Cortisol/DHEA ratio in HIV, HIV-TB, IRIS, HIV-LTB and HD.A. DHEA, B. DHEA-s, C. Cortisol and D. Cortisol/DHEA (ratio) levels in plasma of HIV+, HIV-TB, IRIS, HIV-LTB, and HD individuals. Bars indicate the mean ± SEM for each group. Horizontal lines indicate comparisons between groups and statistically significant differences. DHEA was measured by radioimmunoassay, DHEA-s by immunochemoluminiscence tests and Cortisol by electrochemiluminescence. HIV+ individuals n = 10, HIV-TB n = 21, IRIS n = 6, HIV-LTB n = 5, and HD n = 16. *: p < 0.05; **: p < 0.01; ***: p < 0.001.
Mentions: In order to determine an association of DHEA, DHEA-s and cortisol levels with HIV-TB, IRIS, HIV+ or HIV-LTB conditions, we initially assessed adrenal hormone levels in plasma from patients and healthy donors (HD). Previously, we observed a profound decrease in DHEA levels in TB patients, in parallel to an increase in cortisol [25], We observed that DHEA plasma levels were significantly diminished in HIV-TB and IRIS patients compared to HD, HIV-LTB and HIV+ individuals (p<0.05), whereas DHEA-s levels were markedly diminished in HIV-TB with IRIS individuals (p<0.01 compared to HD, Fig. 1A y 1B). Furthermore, cortisol values were similar among groups except for HIV+ persons, whose cortisol levels were significantly lower compared to HIV-TB patients (p<0.05, Fig. 1C). When analyzing the cortisol/DHEA ratio, co-infected patients and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals (p<0.001, p<0.05, p<0.05 respectively, Fig. 1D), with HIV+ and HIV-LTB patients displaying slightly but still statistically significant lower cortisol/DHEA ratio than HD (p<0.01 and p<0.05 respectively, Fig. 1D).

Bottom Line: DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals.HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals.We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, National Reference Center for AIDS, University of Buenos Aires School of Medicine, Buenos Aires, Argentina. fquiroga@fmed.uba.ar

ABSTRACT
Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

Show MeSH
Related in: MedlinePlus