4 research outputs found
Evidence for a More Disrupted Immune-Endocrine Relation and Cortisol Immunologic Influences in the Context of Tuberculosis and Type 2 Diabetes Comorbidity
Pulmonary tuberculosis (PTB), caused by Mycobacterium tuberculosis (Mtb), is a major health problem worldwide, further aggravated by the convergence of type 2 diabetes mellitus (DM) which constitutes an important risk factor for TB development. The worse scenario of patients with PTB and DM may be partly related to a more unbalanced defensive response. As such, newly diagnosed PTB patients with DM (TB+DM, n = 11) or not (TB, n = 21), as well as DM (n = 18) patients and pair matched controls (Co, n = 22), were investigated for the circulating immuno-endocrine-metabolic profile (ELISA), along with studies in peripheral blood mononuclear cells (PBMC) analyzing transcript expression (RT-qPCR) of mediators involved in glucocorticoid functionality. Given the hyperglycemic/hypercortisolemic scenario of TB+DM patients, PBMC were also exposed to stress-related cortisol concentrations (0.1 and 1 ÎĽM) and supraphysiologic glucose doses (10, 20, and 40 mM) and assessed for the specific response against Mtb stimulation (lymphoproliferation, -thymidine incorporation-, and cytokine production -bead-cytometry). All TB patients displayed increased plasma amounts of cortisol, growth hormone -hGH-, and proinflammatory mediators. In turn, TB+DM showed even higher levels of interferon gamma -IFN-Îł- and hGH (vs. TB), or IL-6, C reactive protein, cortisol and hGH (vs. DM). Both DM groups had equally augmented values of IL-10. All TB patients showed decreased dehydroepiandrosterone- sulfate concentrations, even more in TB+DM cases. Leptin was also decreased in both TB cases, particularly in the TB group, revealing a lower body mass index, as well. Unlike PBMC from TB cases showing a decreased relationship between the glucocorticoids receptor (GR) isoforms (GRα/GRβ; functional isoform/negative isoform), cells from TB+DM patients had no changes in this regard, along with an increased expression of 11-beta hydroxysteroid dehydrogenase type-1, the enzyme facilitating intracellular cortisone to cortisol conversion. TB+DM patients also showed an increased Mtb antigen-driven lymphoproliferation. Compared to TB, DM and HCo counterparts, PBMC from TB+DM patients had a biased Th1 response to Mtb stimulation (increased IL-2 and IFN-Îł production), even when exposed to inhibitory cortisol doses. TB+DM patients show a more unbalanced immuno-endocrine relationship, respect the non-diabetic counterparts, with a relative deficiency of cortisol immunomodulatory influences, despite their more favorable microenvironment for cortisol-mediated immune effects.Fil: Fernández, RocĂo del Valle. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: DĂaz, Ariana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Bongiovanni, Bettina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Gallucci, Georgina Florencia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: BĂ©rtola, Diego. Universidad Nacional de Rosario; ArgentinaFil: Gardeñez, Walter. Universidad Nacional de Rosario; ArgentinaFil: Lioi, Susana. Hospital Provincial del Centenario; ArgentinaFil: Bertolin, YĂ©sica. Hospital Provincial del Centenario; ArgentinaFil: Galliano, Romina. Hospital Provincial del Centenario; ArgentinaFil: Bay, Maria Luisa. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: D'attilio, Luciano David. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; Argentin
Levels of inflammatory cytokines, adrenal steroids, and mRNA for GRα, GRβ and 11βHSD1 in TB pleurisy
Our previous work on the immune-endocrine features of patients with pulmonary tuberculosis (TB) showed markedly decreased plasma levels of dehydroepiandrosterone (DHEA) together with augmented concentrations of Cortisol and pro- and anti-inflammatory cytokines. Studies in peripheral blood mononuclear cells (PBMC) indicated a lower mRNA α/β ratio of glucocorticoid receptors -GR- together with a higher 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) mRNA expression in cases with severe pulmonary TB. Since Pleural TB (PLTB) is a rather benign manifestation of TB, we now analyzed the systemic and local immune-endocrine profile as well as the GRα, GRβ, 11βHSD1 and 11βHSD2 transcripts in PBMC and pleural effusion mononuclear cells (PEMC) of patients with PLTB. PLTB patients had increased levels of IL-1β, IL-6 and IFNÎł together with reduced Cortisol and DHEA concentrations in pleural fluids. Also, a significantly increased expression of 11βHSD1 and GRα was found in PEMC compared to PBMC. Findings point out to an appropriate immune response and a substantial inflammatory reaction, wherein the low Cortisol concentrations may be equally effective, because of the increased expression of GRα and 11βHSD1 transcripts which may optimize the immunomodulatory properties of Cortisol.Fil: D'attilio, Luciano David. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: DĂaz, Ariana. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Santucci, Natalia EstefanĂa. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Bongiovanni, Bettina. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Gardeñez, Walter. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Marchesini, Marcela. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital "Mayor Gabriel Carrasco"; ArgentinaFil: BoguĂ©, Cristina. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: DĂdoli, Griselda. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa; ArgentinaFil: Bottasso, Oscar Adelmo. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Bay, Maria Luisa. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa; Argentin
The clinical recovery of tuberculosis patients undergoing specific treatment is associated with changes in the immune and neuroendocrine responses
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a health problem worldwide. Patients with pulmonary TB show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (DHEA) levels. Extending these findings, we now investigated the immune-endocrine profile of TB patients undergoing specific treatment. Patients (n = 24) were bled at diagnosis (T0), 2, 4, 6 months after treatment initiation and 3 months following its completion. At T0, TB patients showed increased plasma levels of interleukin-6 (IL-6), C reactive protein, interferon-gamma (IFN-Îł) and transforming growth factor beta (TGF-β). These mediators decreased during treatment, reaching levels similar to those from healthy controls (n = 26). Specific treatment led to an increased lymphoproliferative response along with clinical improvement. Newly diagnosed patients had low levels of DHEA, with increased cortisol amounts and cortisol/DHEA ratio, which normalized upon specific treatment. As regards glucocorticoid receptors (GR), TB patients at diagnosis presented a reduced mRNA GRα/GRβ ratio in their peripheral blood mononuclear cells. Furthermore, multivariate analysis showed that cortisol/DHEA ratio was positively associated with inflammatory mediators for which this ratio may constitute a disease biomarker. Anti-mycobacterial treatment results in a better immune-endocrine scenario for the control of physiopathological processes accompanying disease development and hence implied in clinical recovery.Fil: DĂaz, Ariana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Bongiovanni, Bettina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: D'attilio, Luciano David. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Santucci, Natalia EstefanĂa. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: DĂdoli, Griselda. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Fernández, RocĂo del Valle. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Kovalevski, Leandro. Universidad Nacional de Rosario. Facultad de Ciencias EconĂłmicas y EstadĂstica; ArgentinaFil: Lioi, Susana. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Gardeñez, Walter. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Brandan, Nadia. Hospital Escuela Eva PerĂłn; ArgentinaFil: Nannini, Luis J.. Hospital Escuela Eva PerĂłn; ArgentinaFil: Besedovsky, Hugo. Philipps University; AlemaniaFil: del Rey, Adriana. Philipps University; AlemaniaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Bay, Maria Luisa. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; Argentin