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Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection

da Silva et al., Frontiers in Immunology, doi:10.3389/fimmu.2024.1456634
Oct 2024  
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In Silico, In Vitro, and mouse study showing immunomodulatory effects of bovine lactoferrin (bLf) during SARS-CoV-2 infection. In Silico analysis showed bLf strongly binds to TLR4 and NF-kB. In Vitro, bLf modulated frequencies of NK and T cell subsets and cytokine levels in PBMCs from COVID-19 patients. In SARS-CoV-2 infected K18-hACE2 mice, bLf treatment increased pro-inflammatory cytokines systemically and in the lungs, and homeostatic iron metabolism in the brain. Results suggest bLf's immunomodulatory effects depend on infection stage, with pro-inflammatory effects in acute infection and normalization of circulating immune cells in convalescence. Authors propose bLf as a potential supportive immunomodulatory therapy for COVID-19 to promote immune homeostasis.
17 preclinical studies support the efficacy of lactoferrin for COVID-19:
da Silva et al., 17 Oct 2024, USA, peer-reviewed, 24 authors.
This PaperLactoferrinAll
Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection
Andrea Marques Vieira Da Silva, Thiago Lazari Machado, Ryann De Souza Nascimento, Miguel Pires Medeiros Diniz Rodrigues, Felipe Soares Coelho, Luciana Neves Tubarão, Lorenna Carvalho Da Rosa, Camilla Bayma, Vanessa Pimenta Rocha, Ana Beatriz Teixeira Frederico, Jane Silva, Danielle Regina De Almeida De Brito E Cunha, Alessandro Fonseca De Souza, Raphaela Barbosa Gonçalves De Souza, Caroline Augusto Barros, Danielle Da Silva Fiscina, Luiz Claudio Pereira Ribeiro, Carlos Alberto Marques De Carvalho, Bruno Jorge Duque Da Silva, Rodrigo Muller, Tamiris Azamor, Juliana Gil Melgaço, Rafael Braga Gonçalves, Ana Paula Dinis Ano Bom
Frontiers in Immunology, doi:10.3389/fimmu.2024.1456634
Introduction: Lactoferrin (Lf) is an important immunomodulator in infections caused by different agents. During SARS-CoV-2 infection, Lf can hinder or prevent virus access to the intracellular environment. Severe cases of COVID-19 are related to increased production of cytokines, accompanied by a weak type 1 interferon response. Methods: We investigated the influence of bovine Lf (bLf) in the immune response during SARS-CoV-2 infection in vitro and in vivo assays. Results: Our results show a strong binding between bLf and TLR4/NF-kB in silico, as well as an increase in mRNA expression of these genes in peripheral blood mononuclear cells (PBMCs) treated with bLf. Furthermore, the treatment increased TLR4/TLR9 mRNA expression in infected K18-hACE2 mouse blood, indicating an activation of innate response. Our results show that, when bLf was added, a reduction in the NK cell population was found, presenting a similar effect on PD-1 in TCD4 + and TCD8 + cells. In the culture supernatant of PBMCs from healthy participants, bLf decreased IL-6 levels and increased CCL5 in COVID-19 participants. In addition, K18-hACE2 mice infected and treated with bLf presented an increase of serum pro-inflammatory markers (GM-CSF/IL-1b/ Frontiers in Immunology frontiersin.org 01
Ethics statement The studies involving humans were approved by Institutional Review Board under certificate number 37079320. 4 Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456634/ full#supplementary-material
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Severe cases of COVID-19 are ' 'related to increased production of cytokines, accompanied by a weak type 1 interferon ' 'response.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We ' 'investigated the influence of bovine Lf (bLf) in the immune response during SARS-CoV-2 ' 'infection <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> ' 'assays.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Our results show ' 'a strong binding between bLf and TLR4/NF-κB <jats:italic>in silico</jats:italic>, as well as ' 'an increase in mRNA expression of these genes in peripheral blood mononuclear cells (PBMCs) ' 'treated with bLf. Furthermore, the treatment increased <jats:italic>TLR4/TLR9</jats:italic> ' 'mRNA expression in infected K18-hACE2 mouse blood, indicating an activation of innate ' 'response. Our results show that, when bLf was added, a reduction in the NK cell population ' 'was found, presenting a similar effect on PD-1 in TCD4<jats:sup>+</jats:sup> and ' 'TCD8<jats:sup>+</jats:sup> cells. In the culture supernatant of PBMCs from healthy ' 'participants, bLf decreased IL-6 levels and increased CCL5 in COVID-19 participants. In ' 'addition, K18-hACE2 mice infected and treated with bLf presented an increase of serum ' 'pro-inflammatory markers (GM-CSF/IL-1β/IL-2) and upregulated mRNA expression of ' '<jats:italic>IL1B</jats:italic> and <jats:italic>IL6</jats:italic> in the lung tissue. 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Immunol.', 'published': {'date-parts': [[2024, 10, 17]]}}
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