Article
Changes in inflammatory protein and lipid mediator profiles persist after antitubercular treatment of pulmonary and extrapulmonary tuberculosis: a prospective cohort study
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VINHAES, Caian Leal de Azevedo et al. Changes in inflammatory protein and lipid mediator profiles persist after antitubercular treatment of pulmonary and extrapulmonary tuberculosis: a prospective cohort study. Cytokine, v. 123, p. 1-12, 2019.
1043-4666
10.1016/j.cyto.2019.154759
Autor
Vinhaes, Caian Leal de Azevedo
Souza, Deivide Oliveira de
Mattos, Paulo Sérgio de Morais da Silveira
Nogueira, Betania
Shi, Ruiru
Wei, Wang
Yuan, Xing
Zhang, Guolong
Cai, Ying
Barry, Clifton E.
Via, Laura E.
Fukutani, Kiyoshi Ferreira
Andrade, Bruno de Bezerril
Barber, Katrin D. Mayer
Resumen
Intramural Research Program of
the NIAID to K.D.M.B. and C.E.B. The work of B.B.A. was supported by
grants from the NIH (U01AI115940, R01AI069923-08, R01AI20790-
02), by Intramural Program of Fundação Oswaldo Cruz, Fundação José
Silveira and by the Brazilian National Council for Scientific and
Technological Development (CNPq). P.S.S.M. was supported by a PhD
fellowship from the Fundação de Amparo à Pesquisa do Estado da Bahia
(FAPESB). K.F.F. received a fellowship from the Programa Nacional de
Pós-Doutorado, Coordenação de Aperfeiçoamento de Pessoal de Nível
Superior (CAPES) (Finance Code 001). C.L.V. and D.O.S. are supported
by CNPq and FAPESB respectively. 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.