TNF-α blockade impairs in vitro tuberculous granuloma formation and down modulate Th1, Th17 and Treg cytokines

Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclon...

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Bibliographic Details
Published in:PloS one 2018-03, Vol.13 (3), p.e0194430-e0194430
Main Authors: Silva, Djalma A Alves da, Silva, Marcos V da, Barros, Cleyson C Oliveira, Alexandre, Patrícia B Dias, Timóteo, Rodolfo P, Catarino, Jonatas S, Sales-Campos, Helioswilton, Machado, Juliana R, Rodrigues, Denise B R, Oliveira, Carlo J, Rodrigues, Virmondes
Format: Article
Language:English
Subjects:
Activation
Antigens
Arthritis
Bacillus Calmette-Guerin vaccine
BCG
Beads
Biology and Life Sciences
Chemokines
Cytokines
Disease
Disease control
Gene expression
Granuloma
Granulomas
Helper cells
Immunology
Infections
Inflammatory diseases
Infliximab
Interleukin 10
Interleukin 12
Interleukin 17
Laboratories
Leukocytes (mononuclear)
Lymphocytes T
Medical treatment
Medicine and Health Sciences
Monoclonal antibodies
Mycobacterium
Mycobacterium tuberculosis
Nitric oxide
Patients
Peripheral blood mononuclear cells
Tuberculosis
Tumor necrosis factor-TNF
Tumor necrosis factor-α
γ-Interferon
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Summary:Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients. We evaluated 76 individuals, with tuberculosis active, treated and subjects with positive PPD. Granuloma formation was induced in the presence or absence of Infliximab for up to 10 days. The use of Infliximab in cultures significantly blocked TNF-α production (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0194430