tetano
Editor, Senior Moderator
Front Immunol
. 2023 Dec 13:14:1308477.
doi: 10.3389/fimmu.2023.1308477. eCollection 2023. Taming the SARS-CoV-2-mediated proinflammatory response with BromAc[SUP]®[/SUP]
Geovane Marques Ferreira[SUP] 1 [/SUP], Felipe Alves Clarindo[SUP] 1 [/SUP], Ágata Lopes Ribeiro[SUP] 1 [/SUP], Letícia Gomes-de-Pontes[SUP] 1 [/SUP], Luciana Debortoli de Carvalho[SUP] 2 [/SUP], Olindo Assis Martins-Filho[SUP] 3 [/SUP], Flávio Guimarães da Fonseca[SUP] 1 4 [/SUP], Mauro Martins Teixeira[SUP] 5 [/SUP], Adriano de Paula Sabino[SUP] 6 [/SUP], Mathew Suji Eapen[SUP] 7 [/SUP], David L Morris[SUP] 7 8 9 [/SUP], Sarah J Valle[SUP] 7 8 10 [/SUP], Jordana Grazziela Alves Coelho-Dos-Reis[SUP] 1 5 [/SUP]
Affiliations
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.
Keywords: BromAc; COVID-19; anti-inflammatory; cytokine storm; immunomodulatory; therapeutic strategy.
. 2023 Dec 13:14:1308477.
doi: 10.3389/fimmu.2023.1308477. eCollection 2023. Taming the SARS-CoV-2-mediated proinflammatory response with BromAc[SUP]®[/SUP]
Geovane Marques Ferreira[SUP] 1 [/SUP], Felipe Alves Clarindo[SUP] 1 [/SUP], Ágata Lopes Ribeiro[SUP] 1 [/SUP], Letícia Gomes-de-Pontes[SUP] 1 [/SUP], Luciana Debortoli de Carvalho[SUP] 2 [/SUP], Olindo Assis Martins-Filho[SUP] 3 [/SUP], Flávio Guimarães da Fonseca[SUP] 1 4 [/SUP], Mauro Martins Teixeira[SUP] 5 [/SUP], Adriano de Paula Sabino[SUP] 6 [/SUP], Mathew Suji Eapen[SUP] 7 [/SUP], David L Morris[SUP] 7 8 9 [/SUP], Sarah J Valle[SUP] 7 8 10 [/SUP], Jordana Grazziela Alves Coelho-Dos-Reis[SUP] 1 5 [/SUP]
Affiliations
- PMID: 38193087
- PMCID: PMC10773902
- DOI: 10.3389/fimmu.2023.1308477
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.
Keywords: BromAc; COVID-19; anti-inflammatory; cytokine storm; immunomodulatory; therapeutic strategy.