Vitamin D deficiency in relation with the systemic and central inflammation during multiple sclerosis

J Med Biochem. 2023 Aug 25;42(3):364-375. doi: 10.5937/jomb0-37676.

Abstract

Background: During the last decade, vitamin D (VitD) has become a topic of interest in immune regulation, especially in multiple sclerosis (MS) disease. Amongst the wide range of effects reported for this vitamin on the immune system, a regulatory role on cytokines production has been described. Our aim is to analyze the status of VitD and its correlation with the circulating inflammation and the intrathecal humoral response during MS.

Methods: We analyzed samples of 318 individuals: 108 MS patients and 210 controls. Determination of 25-(OH) VitD3 level in serum was made using electrochemiluminescence method. Circulating inflammatory cytokines (IL-6, IL-8, IL-10, TNF-a, IL12p70 and IL-1b) were investigated using Cytometer Bead Array Technology. The central humoral response was characterized using CSF isofocusing test and IgG Index calculation.

Results: As expected, mean value of VitD was significantly lower in MS group (26 nmol/L) than in control group (34.75 nmol/L) (p=0.002), with a severe deficiency in 67% of MS patients. Mean value of VitD was significantly lower in MS female patients. Regarding cytokines, mean value of TNFa was significantly higher in MS patients with oligoclonal bands of IgG in the CSF. IL6 was positively correlated with IgG level in serum of MS patients.

Conclusions: Our results support the association of VitD deficiency with MS, especially in female patients of our region. However, the vitamin level seems to not correlate with inflammatory cytokines nor with disability. Interestingly, TNFa and IL6 levels were correlated with the intrathecal synthesis of IgG and the circulating IgG level, respectively.

Uvod: Tokom poslednje decenije, vitamin D (VitD) je postao tema od interesa za regulaciju imuniteta, posebno kod bolesti multiple skleroze (MS). Među širokim spektrom efekata prijavljenih za ovaj vitamin na imuni sistem, opisana je regulatorna uloga u proizvodnji citokina. Naš cilj je bio da analiziramo status VitD i njegovu korelaciju sa cirkulišućom inflamacijom i intratekalnim humoralnim odgovorom tokom MS.

Metode: Analizirali smo uzorke od 318 osoba: 108 pacijenata sa MS i 210 kontrola. Određivanje nivoa 25-(OH) VitD3 u serumu je izvršeno metodom elektrohemiluminiscencije. Cirkulišući inflamatorni citokini (IL-6, IL-8, IL-10, TNF-a, IL12p70 i IL-1b) su ispitivani korišćenjem Citometer Bead Array Technology. Centralni humoralni odgovor je okarakterisan korišćenjem testa izofokusiranja CSF i izračunavanja IgG indeksa.

Rezultati: Kao što se i očekivalo, srednja vrednost VitD je bila značajno niža u grupi sa MS (26 nmol/L) nego u kontrolnoj grupi (34,75 nmol/L) (p=0,002), sa teškim nedostatkom kod 67% pacijenata sa MS. Srednja vrednost VitD bila je značajno niža kod pacijenata sa MS. Što se tiče citokina, srednja vrednost TNFa je bila značajno viša kod pacijenata sa MS sa oligoklonalnim trakama IgG u CSF. IL6 je bio u pozitivnoj korelaciji sa nivoom IgG u serumu pacijenata sa MS.

Zaključak: Naši rezultati podržavaju povezanost deficita VitD sa MS, posebno kod pacijenata našeg regiona. Međutim, čini se da nivo vitamina nije u korelaciji sa inflamatornim citokinima niti sa invaliditetom. Zanimljivo je da su nivoi TNFa i IL6 bili u korelaciji sa intratekalnom sintezom IgG i nivoom IgG u cirkulaciji, respektivno.

Keywords: CSF oligoclonal bands; inflammatory cytokines; multiple sclerosis; vitamin D.