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CHANGES IN INFLAMMATORY PROTEIN AND LIPID MEDIATOR PROFILES PERSIST AFTER ANTITUBERCULAR TREATMENT OF PULMONARY AND EXTRAPULMONARY TUBERCULOSIS: A PROSPECTIVE COHORT STUDY
Mediador lipídico
Inflamação
Mycobacterium tuberculosis
Bacilos ácido-resistentes
Tuberculose extrapulmonar
Lipid mediator
Inflammation
Mycobacterium tuberculosis
Acid-fast bacilli
Extrapulmonary tuberculosis
Autor(es)
Afiliação
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Henan Chest Hospital. Zhengzhou, China.
Henan Chest Hospital. Zhengzhou, China.
Henan Chest Hospital. Zhengzhou, China.
Henan Anti-TB Institute. Sino-US Joint Research Laboratory for Tuberculosis of Henan. Zhengzhou, China.
Henan Anti-TB Institute. Sino-US Joint Research Laboratory for Tuberculosis of Henan. Zhengzhou, China.
Henan Anti-TB Institute. Sino-US Joint Research Laboratory for Tuberculosis of Henan. Zhengzhou, China.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine. Nashville, USA.
National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, USA.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Henan Chest Hospital. Zhengzhou, China.
Henan Chest Hospital. Zhengzhou, China.
Henan Chest Hospital. Zhengzhou, China.
Henan Anti-TB Institute. Sino-US Joint Research Laboratory for Tuberculosis of Henan. Zhengzhou, China.
Henan Anti-TB Institute. Sino-US Joint Research Laboratory for Tuberculosis of Henan. Zhengzhou, China.
Henan Anti-TB Institute. Sino-US Joint Research Laboratory for Tuberculosis of Henan. Zhengzhou, China.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine. Nashville, USA.
National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, USA.
Resumo em Inglês
Background: The identification of meaningful biomarkers of tuberculosis (TB) has potential to improve diagnosis, disease staging and prediction of treatment outcomes. It has been shown that active pulmonary TB (PTB) is
associated with qualitative and quantitative changes in systemic immune profile, suggesting a chronic inflammatory imbalance. Here we characterized the profile of PTB and extrapulmonary TB (EPTB) in a prospective cohort study. Methods: We measured a panel of 27 inflammatory cytokines, soluble receptors, and lipid mediators in peripheral blood from patients with PTB or EPTB from a prospective clinical study in China. Multidimensional analyses were performed to describe associations between plasma levels of biomarkers and different TB disease presentation profiles. Results: Mycobacterium tuberculosis infection induced changes in both the expression and correlation profiles of plasma mediators of inflammation in patients with PTB compared to those with EPTB. Increases in mycobacterial loads in sputum smears were associated with rises in concentrations of several molecules involved in TB pathogenesis, such as IL-1β, IFN-α, IL-10 and PGF2α. Moreover, PTB patients presenting with severe disease exhibited a distinct inflammatory profile hallmarked by heightened levels of TNF-α, IL-1β, IL17, IL-18 and IL-27. Interestingly, while antitubercular treatment (ATT) resulted in early changes of plasma concentrations of markers in PTB, changes were delayed in EPTB patients. Exploratory analyses of the molecular degree of perturbation (MDP) of the inflammatory mediators before and during ATT suggested the occurrence of infection and/or treatment-induced long lasting “inflammatory imprinting” of biomarker profiles in TB. At 24 weeks post ATT commencement, markers underlying the observed increases in MDP scores were IL-27 in PTB and IL-1β in EPTB patients. Conclusion: Our findings describe systemic and durable changes in the concentrations of inflammatory cytokines and lipid mediators in both PTB and EPTB and emphasize the role of M. tuberculosis bacterial burden and site of disease in modulating patient immune biomarkers.
Palavras-chave
CitocinasMediador lipídico
Inflamação
Mycobacterium tuberculosis
Bacilos ácido-resistentes
Tuberculose extrapulmonar
Palavras-chave em inglês
CytokinesLipid mediator
Inflammation
Mycobacterium tuberculosis
Acid-fast bacilli
Extrapulmonary tuberculosis
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