Title Imunomodulacijski učinci vitamina D u prevenciji infekcije SARS-CoV-2
Title (english) Immunomodulatory effects of vitamin D in prevention of SARS-CoV 2 infection
Author Tara Vuletić
Mentor Robert Likić (mentor)
Committee member Milan Milošević (predsjednik povjerenstva)
Committee member Marko Jakopović (član povjerenstva)
Committee member Robert Likić (član povjerenstva)
Granter University of Zagreb School of Medicine (Department of Internal Medicine) Zagreb
Defense date and country 2021-09-02, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Internal Medicine
Abstract Vitamin D molekula je topiva u mastima koja iz 7-dehidrokolesterola nastaje u koži pod utjecajem UVB zračenja i unosi se prehranom u obliku kolekaciferola ili ergokalciferola. Vitamin D nastao kožnom sintezom 25-hidroksilacijom i 1-alfa-hidroksilacijom pomoću CYP2R1 i CYP27B1 enzima prelazi u metabolički aktivne oblike. U složenoj regulaciji metabolizma vitamina D sudjeluju on sam autoregulatorno, minerali kalcij i fosfor, mnogi hormoni, a najznačajnije PTH i FGF23. U plazmi se vitamin D i njegovi metaboliti nalaze vezani za protein koji veže vitamin D. Poluvijek eliminacije ovisi o afinitetu pojedinog metabolita prema DBP-u. Eliminacija se većinski odvija putem žuči, a višak je pohranjen u masnom tkivu. Vitamin D učinke ostvaruje vežući se na unutarstanični receptor za vitamin D koji tvori heterodimer s retinoid-X receptorom i u jezgri se veže na specifične sljedove DNK u promotorskoj regiji gena, tzv. elemente odgovora. Posljedično utječe na transkripciju oko dvije stotine ciljnih gena uključujući i gen za vlastiti receptor. Vitamin D regulira metabolizam minerala kalcija i fosfora, proliferaciju i diferencijaciju stanica uključujući stanice imunološkog sustave i maligne stanice. Prema EFDA-i optimalna razina 25-hidroksivitamina D u serumu iznosi 50nmol/L za sve dobne skupine. Preporučeni dnevni unos vitamina D iznosi 600 IU za odrasle osobe, trudnice i djecu stariju od godinu dana te 400 IU za djecu do godinu dana starosti. Manjak vitamina D javlja se
zbog nedovoljne izloženosti Sunčevoj svjetlosti, nedovoljnog unosa, smanjene apsorpcije ili poremećenog metabolizma. Očituje se kao rahitis, osteomalacija ili patološkim prijelomima ovisno o životnoj dobi pacijenta. Makrofazi, dendritičke stanice, limfociti T i limfociti B eksprimiraju VDR receptor. Vitamin D modulira odgovor urođene i stečene imunosti na antigene, kontrolira opseg upalnog odgovora, smanjuje lučenje proupalnih citokina i imunoglobulina, potiče stvaranje i lučenje baktericidnih proteina. Manjak vitamina D povezuje se sa smanjenom otpornošću na infekcije i autoimunošću. U brojnim je bolestima autoimune etiologije vitamin D pokazao potencijal kao dopuna standardnoj terapiji. Adekvatna razina vitamina D djeluje protektivno u prevenciji akutnih respiratornih infekcija uključujući infekciju SARS-CoV-2 virusom. Taj je učinak osobito izražen u skupinama s
deficijencijom vitamina D i kad se suplementacija primjenjuje u dnevnom ili tjednom režimu, ali ne i bolus dozi. Broj oboljelih veći je u hladnijem dijelu godine i među osobama tamnije puti zbog manje apsorpcije UVB. Ulazno mjesto SARS-CoV-2 je ACE-2 na površini stanica. Virus kompromitira funkciju ACE-2 što rezultira pretjeranom vazokonstrikcijom, oštećenjem tkiva i endotela. Teški klinički oblici COVID-a obilježeni su disregulacijom imunološkog odgovora i citokinskom olujom, a primjena vitamina D pokazala se uspješnom u snižavanju razine IL-6 koji je povezan s komplikacijama i lošim ishodom bolesti. Potrebna su dodatna istraživanja za potvrdu i preciznu procjenu terapijskih učinaka i najpogodnije doze vitamina D u liječenju COVID-a 19.
Abstract (english) Vitamin D is a fat-soluble molecule synthesized from 7-dehydrocholesterol in the skin exposed to UVB radiation. Two forms are obtained by diet – colecaciferol and ergocalciferol. Vitamin D formed through skin synthesis undergoes 25-hydroxylation and 1-alpha-hydroxylation by CYP2R1 and CYP27B1 enzymes to be converted into metabolically active forms. Levels of
minerals calcium and phosphorus and many hormones, mainly PTH and FGF23 affect vitamin D metabolism which is autoregulated as well. In plasma, vitamin D binding protein transports vitamin D and its metabolites. The elimination half-life varies depending on each metabolite affinity for DBP and takes place mostly through the bile. The excess is stored in adipose tissue. Vitamin D effects are mediated through binding to the intracellular VDR, which then forms a heterodimer with the RXR which binds to specific DNA sequences in the promoter region of the gene, the so-called response elements. Consequently, it affects the transcription of about two hundred target genes including the gene for its own receptor.
Vitamin D regulates the metabolism of the minerals calcium and phosphorus, cell proliferation and differentiation including immunological and malignant cells. According to the EFDA, the desirable serum level of 25-OH-vitamin D is 50nmol/L in all age groups. The RDA for vitamin D counts 600 IU for adults, pregnant women and all children except 400 IU for children up to one year of age. Vitamin D deficiency occurs due to insufficient exposure to sunlight, low intake, reduced absorption or impaired metabolism. It clinically manifests as rickets, osteomalacia, or pathological fractures depending on the patients' age. Macrophages, dendritic cells, T lymphocytes, and B lymphocytes express the VDR on the surface. Vitamin D modulates the innate and acquired immune response to antigens, controls the extent of the inflammation, reduces the secretion of proinflammatory cytokines and immunoglobulins, stimulates the production and secretion of bactericidal proteins. Vitamin D deficiency is associated with reduced resistance to infections and autoimmunity. In a number of diseases of autoimmune etiology, vitamin D has shown potential as an adjuvant option to standard therapy. Adequate vitamin D levels act protectively regarding prevention of acute respiratory infections including SARS-CoV-2 infection. This effect is particularly noticeable in population with vitamin D deficiency and when supplementation is administered on a daily or weekly basis but not a bolus dose. The number of infected patients is higher during the colder part of the year and among people with darker complexion due to lower UVB absorption. The entry point of SARS-CoV-2 is ACE-2 at the cell surface. The virus compromises the function of ACE-2 resulting in excessive vasoconstriction, tissue and endothelial damage. Severe clinical forms of COVID are characterized by impaired regulation of the immune response and cytokine
storm. The administration of vitamin D has been shown to be successful in lowering IL-6 levels associated with complications and poor disease outcome. Further research is needed to confirm and accurately assess the therapeutic effects of vitamin D in the treatment of COVID 19.
Keywords
vitamin D
SARS-CoV-2
COVID-19
imunomodulacija
imunološki sustav
Keywords (english)
vitamin D
SARS-CoV-2
COVID-19
immunomodulation
immune system
Language croatian
URN:NBN urn:nbn:hr:105:022855
Study programme Title: Medicine Study programme type: university Study level: integrated undergraduate and graduate Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Created on 2022-05-20 09:57:19