Author | Ferreira, Geovane Marques | |
Author | Clarindo, Felipe Alves | |
Author | Ribeiro, Ágata Lopes | |
Author | Gomes-de-Pontes, Letícia | |
Author | Carvalho, Luciana Debortoli de | |
Author | Martins Filho, Olindo Assis | |
Author | Fonseca, Flávio Guimarães da | |
Author | Teixeira, Mauro Martins | |
Author | Sabino, Adriano de Paula | |
Author | Eapen, Mathew Suji | |
Author | Morris, David L | |
Author | Valle, Sarah J | |
Author | Coelho-Dos-deis, Jordana Grazziela Alves | |
Access date | 2024-01-25T19:51:05Z | |
Available date | 2024-01-25T19:51:05Z | |
Document date | 2023 | |
Citation | FERREIRA, Geovane Marques et al. Taming the SARS-CoV-2-mediated proinflammatory response with BromAc. Front Immunol., v. 14, 1308477, 2023. doi: 10.3389/fimmu.2023.1308477. | en_US |
ISSN | 1664-3224 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/62386 | |
Language | eng | en_US |
Publisher | Frontiers Research Foundation | en_US |
Rights | open access | en_US |
Title | Taming the SARS-CoV-2-mediated proinflammatory response with BromAc | en_US |
Type | Article | en_US |
Abstract | Introduction: In the present study, the impact of BromAc®, a specific combination of bromelain and acetylcysteine, on the SARS-CoV-2-specific inflammatory response was evaluated.
Methods: An in vitro stimulation system was standardized using blood samples from 9 healthy donors, luminex assays and flow cytometry were performed.
Results and discussion: BromAc® demonstrated robust anti-inflammatory activity in human peripheral blood cells upon SARS-CoV-2 viral stimuli, reducing the cytokine storm, composed of chemokines, growth factors, and proinflammatory and regulatory cytokines produced after short-term in vitro culture with the inactivated virus (iSARS-CoV-2). A combined reduction in vascular endothelial growth factor (VEGF) induced by SARS-CoV-2, in addition to steady-state levels of platelet recruitment-associated growth factor-PDGFbb, was observed, indicating that BromAc® may be important to reduce thromboembolism in COVID-19. The immunophenotypic analysis of the impact of BromAc® on leukocytes upon viral stimuli showed that BromAc® was able to downmodulate the populations of CD16+ neutrophils and CD14+ monocytes observed after stimulation with iSARS-CoV-2. Conversely, BromAc® treatment increased steady-state HLA-DR expression in CD14+ monocytes and preserved this activation marker in this subset upon iSARS-CoV-2 stimuli, indicating improved monocyte activation upon BromAc® treatment. Additionally, BromAc® downmodulated the iSARS-CoV-2-induced production of TNF-a by the CD19+ B-cells. System biology approaches, utilizing comprehensive correlation matrices and networks, showed distinct patterns of connectivity in groups treated with BromAc®, suggesting loss of connections promoted by the compound and by iSARS-CoV-2 stimuli. Negative correlations amongst proinflammatory axis and other soluble and cellular factors were observed in the iSARS-CoV-2 group treated with BromAc® as compared to the untreated group, demonstrating that BromAc® disengages proinflammatory responses and their interactions with other soluble factors and the axis orchestrated by SARS-CoV-2.
Conclusion: These results give new insights into the mechanisms for the robust anti-inflammatory effect of BromAc® in the steady state and SARS-CoV-2-specific immune leukocyte responses, indicating its potential as a therapeutic strategy for COVID-19. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Laboratório de Virologia Básica e Aplicada. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Laboratório de Virologia Básica e Aplicada. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Laboratório de Virologia Básica e Aplicada. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Laboratório de Virologia Básica e Aplicada. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Universidade Estadual de Santa Cruz. Departamento de Biologia e Biotecnologia de Microrganismos. Ilhéus, BA, Brazil. | en_US |
Affilliation | Grupo Integrado de Pesquisas em Biomarcadores. Rene Rachou Institute, Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Laboratório de Virologia Básica e Aplicada. Belo Horizonte, MG, Brazil/Parque Tecnológico de Belo Horizonte. Centro de Tecnologia em Vacinas Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Universidade Federal de Minas Gerais. CT Terapias Avançadas e Inovadoras. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Laboratório de Hematologia Clínica, Experimental e Molecular. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Research & Development Department. Mucpharm Pty Ltd. Sydney, NSW, Australia. | en_US |
Affilliation | Research & Development Department. Mucpharm Pty Ltd. Sydney, NSW, Australia/ St George and Sutherland Hospital Clinical School. University of New South Wales. Sydney, NSW, Australia/Department of Surgery. St George Hospital. Sydney, NSW, Australia | en_US |
Affilliation | Research & Development Department. Mucpharm Pty Ltd. Sydney, NSW, Australia/St George and Sutherland Hospital Clinical School. University of New South Wales. Sydney, NSW, Australia/Intensive Care Unit. St George Hospital. Sydney, NSW, Australia. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Laboratório de Virologia Básica e Aplicada. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. CT Terapias Avançadas e Inovadoras. Belo Horizonte, MG, Brazil. | en_US |
Subject | BromAc; | en_US |
Subject | COVID-19 | en_US |
Subject | anti-inflammatory | en_US |
Subject | cytokine storm | en_US |
Subject | immunomodulatory | en_US |
Subject | therapeutic strategy | en_US |