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All Studies   Meta Analysis    Recent:   

Disentangling the Immunomodulatory Effects of Vitamin D on the SARS-CoV-2 Virus by In Vitro Approaches

Alcalá-Santiago et al., The 14th European Nutrition Conference FENS 2023, doi:10.3390/proceedings2023091415
Mar 2024  
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Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
 
*, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,800+ studies for 95 treatments. c19early.org
In Vitro study showing that vitamin D inhibits inflammatory cytokine production in THP-1 cells stimulated with the SARS-CoV-2 spike protein. Authors used vitamin D at doses of 10 and 25 nM to treat THP-1 cells, a human monocytic cell line expressing the ACE2 receptor, after stimulation with low doses of the spike protein. While vitamin D did not affect IL-6 mRNA levels, it downregulated the transcription of pro-inflammatory cytokines IL-1β and TNF-α.
21 preclinical studies support the efficacy of vitamin D for COVID-19:
Vitamin D has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function20-23. Vitamin D inhibits SARS-CoV-2 replication in vitro10,17, mitigates lung inflammation, damage, and lethality in mice with an MHV-3 model for β-CoV respiratory infections10,17, reduces SARS-CoV-2 replication in nasal epithelial cells via increased type I interferon expression13, downregulates proinflammatory cytokines IL-1β and TNF-α in SARS-CoV-2 spike protein-stimulated cells9, attenuates nucleocapsid protein-induced hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway14, may be neuroprotective by protecting the blood-brain barrier, reducing neuroinflammation, and via immunomodulatory effects24, minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling8, and improves regulatory immune cell levels and control of proinflammatory cytokines in severe COVID-1925. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells and vitamin D has been shown to improve NK cell activity26,27.
Alcalá-Santiago et al., 15 Mar 2024, peer-reviewed, 4 authors. Contact: angela.alcala@ugr.es (corresponding author), memolina@ugr.es, nmrodriguez@ig.csic.es, j.pedroche@csic.es.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin DAll
Disentangling the Immunomodulatory Effects of Vitamin D on the SARS-CoV-2 Virus by In Vitro Approaches
Ángela Alcalá-Santiago, Noelia M Rodríguez-Martin, Justo Pedroche, Esther Molina-Montes
doi:10.3390/proceedings2023091415
Vitamin D is a fat-soluble vitamin with multiple functions, including the modulation of the immune response, amongst others. Earlier studies have demonstrated that the active form of vitamin D, 1,25-dihydroxivitamin D, inhibits LPS-induced IL-6 and TNF-α production by human monocytes in a dose-dependent manner. On the other hand, some in vitro studies support that this vitamin has immune modulatory effects on viral infections. However, it remains unclear whether vitamin D regulates the immune response in infectious diseases triggered by viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. This study aimed to evaluate the anti-inflammatory properties of vitamin D against the spike protein of the SARS-CoV-2 virus. For this purpose, vitamin D was used in two different doses of 10 and 25 nM on the THP-1 cell line, which was stimulated with low doses of the SARS-CoV-2 virus spike protein. The THP-1 cell line, which is derived from human monocytic cells, was chosen since it contains the ACE2 transporter of the spike protein. Moreover, it is a widely used model to examine inflammatory processes due to its potential to stimulate inflammation and the release of inflammatory cytokines. The THP-1 cells were incubated for 1 h with the spike protein, subsequently treated with the two selected doses of vitamin D and incubated for 24 h. ELISA and RT-qPCR techniques were used to quantify the levels of inflammatory cytokines. Our results showed that vitamin D had no effect on the mRNA transcriptional levels of cytokine IL-6, but it was able to down-regulate the transcriptional levels of the pro-inflammatory cytokines IL-1β and TNF-α. There was no dose-response relationship between vitamin D and the expression of these genes. In conclusion, vitamin D inhibited inflammatory cytokine production on spike protein-stimulated inflammation in the THP1 cell line. The study is being completed by testing higher doses of vitamin D and of the spike protein. Additionally, other markers of inflammation are being measured through the use of transcriptomic analyses of the control vs. treated THP1 cells.
Conflicts of Interest: The authors declare no conflict of interest. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
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