25-hydroxyvitamin-d-2 and Inflammation

Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways. We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality. Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection. Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection. Covid-19 infection and mortality data was gathered from the World Health Organisation. Results Counter-intuitively, lower latitude and typically 'sunny' countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency. These countries have also been experiencing the highest infection and death rates in Europe. The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates. The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0.046) by Spearman's Rank Correlation. Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19. There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19.

Topics: 25-Hydroxyvitamin D 2; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; Dietary Supplements; Europe; Health Policy; Humans; Inflammation; Pandemics; Pneumonia, Viral; Prevalence; SARS-CoV-2; Severity of Illness Index; Vitamin D; Vitamin D Deficiency

Lower 25-hydroxyvitamin D2 /D3 levels at melanoma diagnosis are associated with thicker primaries and poorer survival. We postulated that this might relate to the deleterious effect of systemic inflammation as 25-hydroxyvitamin D2 /D3 levels are inversely associated with levels of C-reactive protein. 2,182 participants in the Leeds Melanoma Cohort (median follow-up 7.98 years) provided data on drug exposure, comorbidities and a serum 25-hydroxyvitamin D2 /D3 level at recruitment. Factors reported to modify systemic inflammation (low vitamin D levels, high body mass index, use of aspirin or nonsteroidal anti-inflammatory drugs or smoking were tested as predictors of microscopic ulceration (in which primary tumors are inflamed) and melanoma-specific survival (MSS). Ulceration was independently associated with lower 25-hydroxyvitamin D2 /D3 levels (odds ratio (OR) = 0.94 per 10 nmol/L, 95% CI 0.88-1.00, p = 0.05) and smoking at diagnosis (OR = 1.47, 95% CI 1.00-2.15, p = 0.04). In analyses adjusted for age and sex, a protective effect was seen of 25-hydroxyvitamin D2 /D3 levels at diagnosis on melanoma death (OR = 0.89 per 10 nmol/L, 95% CI 0.83-0.95, p < 0.001) and smoking increased the risk of death (OR = 1.13 per 10 years, 95% CI 1.05-1.22, p = 0.001). In multivariable analyses (adjusted for tumor thickness) the associations with death from melanoma were low 25-hydroxyvitamin D2 /D3 level at recruitment (<20 nmol/L vs. 20-60 nmol/L, hazard ratio (HR) = 1.52, 95% CI 0.97-2.40, p = 0.07) and smoking duration at diagnosis (HR = 1.11, 95% CI 1.03-1.20, p = 0.009). The study shows evidence that lower vitamin D levels and smoking are associated with ulceration of primary melanomas and poorer MSS. Further analyses are necessary to understand any biological mechanisms that underlie these findings.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Calcifediol; Comorbidity; Female; Follow-Up Studies; Humans; Inflammation; Male; Melanoma; Middle Aged; Multivariate Analysis; Smoking; Survival Analysis; Treatment Outcome; Ulcer; United Kingdom; Young Adult

The effect of vitamin D pertinent to cardiovascular health on the heart itself is considered to shift toward an anti-inflammatory response in chronic heart failure (CHF); however, its underlying mechanism is not completely understood. In this study, we demonstrated that plasma 25(OH)D level, negatively associated with NT-ProBNP, correlated with the decreased Treg in CHF compared to the patients with other cardiovascular diseases and healthy and older donors. Naïve Treg cell (CD4(+)CD45RA(+)Foxp3(lo)T) subset, rather than whole Treg cells, contributes to the reduction of Treg in CHF. 1,25(OH)2D treatment maintained partial expression of CD45RA on CD4(+)T cell after αCD3/CD28 monoclonal antibodies activation and ameliorated the impaired CD4(+)CD45RA(+)T cell function from CHF patients through upregulating Foxp3 expression and IL-10 secretion in vitro. Low level of vitamin D receptor (VDR) was detected in CD4(+)CD45RA(+)T cell of CHF than control, while 1,25(OH)2D treatment increased the VDR expression to exert its immunosuppression on T cell. The results of this study might provide tangible evidence to our knowledge of the impact of vitamin D supplementation on naïve Tregs, which may offer new means of preventing and treating CHF.

Topics: 25-Hydroxyvitamin D 2; Aged; Anti-Inflammatory Agents; CD4 Antigens; Female; Flow Cytometry; Heart Failure; Humans; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-17; Leukocyte Common Antigens; Lymphocyte Count; Male; Middle Aged; T-Lymphocytes, Regulatory; Th17 Cells; Vitamin D Deficiency

Epidemiological studies have reported that vitamin D deficiency is associated with inflammatory disease. Smoking is a well-known risk factor for inflammation. However, few studies have investigated the interactive effect of vitamin D deficiency and smoking on inflammation. This study aims to investigate the interaction of vitamin D and smoking with inflammatory markers in the urban elderly.. We used data from the Korean Elderly Environmental Panel Study, which began in August 2008 and ended in August 2010, and included 560 Koreans ≥60 years old living in Seoul. Data was collected via questionnaires that included items about smoking status at the first visit. Vitamin D levels, high-sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) counts were repeatedly measured up to three times.. The association of vitamin D and hs-CRP was significant after adjusting for known confounders (β=-0.080, p=0.041). After separate analysis by smoking status, the association of vitamin D deficiency and hs-CRP in smokers was stronger than that in nonsmokers (smokers: β=-0.375, p=0.013; non-smokers: β=-0.060, p=0.150). Smoking status was an effect modifier that changed the association between vitamin D deficiency and hs-CRP (interaction estimate: β=-0.254, p=0.032). Vitamin D was not significantly associated with WBC count (β=0.003, p=0.805).. Vitamin D deficiency was associated with hs-CRP in the urban elderly. Smoking status was an effect modifier of this association. Vitamin D deficiency was not significantly associated with WBC count.

Topics: 25-Hydroxyvitamin D 2; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Leukocyte Count; Male; Middle Aged; Smoking; Urban Population; Vitamin D; Vitamin D Deficiency

The aim of the study was to investigate the concentration of PGRN and other inflammatory cytokines TNF-α, IL-1β, IL-4, IL-6, IL-10, IL-13 and IL-17 in osteopenic and non-osteopenic obese subjects. Bone mineral density in subjects with different PGRN levels were compared to the appraisal of our hypothesis.. A total of 171 obese participants (BMI ≥30) were included in the study. Analysis of body composition was performed with use of Body Composition Analyzer. All blood samples were collected between 8:00 and 10:00 a.m. following an overnight fasting. The circulating levels of TNF-α, PGRN, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, 25-Hydroxy Vitamin D and crosslaps were measured with the EIA method. BMD was measured by use of dual energy X-ray absorptiometery (DXA) at lumbar spine (vertebrae L2-L4) and hip level. Participants were categorized into osteopenic and healthy group according to the World Health Organization (WHO) criteria. Of 171 participants, 51 (29.82 %) were osteopenic and 120 (70.17%) were healthy.. We found significantly higher concentrations of crosslaps, IL-17, IL-6, TNFα and IL-4 and lower concentrations of IL-13, IL-10, PGRN and free fat mass in osteopenic group. With raising the PGRN level, the concentrations of IL-13, IL-10 and 25-(OH) vitamin D were increased and the concentration of TNFα and IL-17 were decreased. Our results demonstrated that the density of bone at both sites of lumbar spine (L2-L4) and hip region was highest in 4th quartile and lowest in first quartile of categorized PGRN concentration. The bone status was gradually improved with raising the PGRN level in parallel at lumbar spine (L2-L4) and hip regions.. Based on the pathway of effect of TNFα on bone metabolism, it appears that PGRN acts on the bone with mechanisms involving TNFR signaling, disturbance and TNFα performance, similar to the results that have been found in animal model study.

Topics: 25-Hydroxyvitamin D 2; Adult; Biomarkers; Body Composition; Bone Density; Bone Diseases, Metabolic; Collagen; Female; Hip; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukins; Iran; Lumbosacral Region; Male; Middle Aged; Obesity; Parathyroid Hormone; Peptide Fragments; Progranulins; Protein Precursors; Receptors, Tumor Necrosis Factor; Spine; Tumor Necrosis Factor-alpha; Young Adult