Vitamin D deficiency is associated with IL-6 levels and monocyte activation in HIV-infected persons

Abstract

BackgroundImmune activation plays a key role in HIV pathogenesis. Markers of inflammation have been associated with vitamin D deficiency in the general population. Studies have also demonstrated associations of vitamin D deficiency with increased risk of HIV progression and death. The relationship between persistent inflammation and immune activation during chronic HIV infection and vitamin D deficiency remains unclear.MethodsCryopreserved specimens were analyzed from 663 participants at the time of enrollment from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) from 2004 to 2006. Biomarkers of inflammation, atherosclerosis, and coagulation were measured using enzyme-linked immunosorbent assays (ELISAs) and electrochemiluminescence. 25(OH)D, the stable precursor form of vitamin D, was measured using a radioimmunoassay with levels defined as: normal (≥30ng/mL), insufficient (20–29 ng/mL) and deficient (<20 ng/mL). Monocyte phenotypes were assessed by flow cytometry. Linear and logistic regression models were used to determine statistical associations between biomarkers and vitamin D deficiency.Results25(OH)D levels were deficient in 251 (38%) participants, insufficient in 222 (34%), and normal in 190 (29%). Patients with vitamin D deficiency, when compared to those with insufficient or normal vitamin D levels, had increased levels of IL-6 (23%; p<0.01), TNF-α (21%, p = 0.03), D-dimer (24%, p = 0.01), higher proportions of CD14dimCD16+ (22%, p<0.01) and CX3CR1+ monocytes (48%; p<0.001) and decreased frequency of CCR2+ monocytes (-3.4%, p<0.001). In fully adjusted models, vitamin D associations with abnormal biomarker levels persisted for IL-6 levels and CX3CR1+ and CCR2+ phenotypes.ConclusionsVitamin D deficiency is associated with greater inflammation and activated monocyte phenotypes. The role of vitamin D deficiency in persistent immune activation and associated complications during chronic HIV disease should be further evaluated as a possible target for intervention.

Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

“…Clinical Severe cases associated with pneumonia Inverse correlation for CAP [68,69] Increased production of pro-inflammatory cytokines such as IL-6 Inverse correlation [70,71] Increased CRP Inverse correlation [72,73] Increased risk of sepsis Inverse correlation [74,75] Risk of ARDS Inverse correlation [76,77] Risk of heart failure Inverse correlation [78,79] Risk of diabetes mellitus Inverse correlation [67,80] Epidemiological Began in December 2019 in China, spread mainly to northern midlatitude countries Low 25(OH)D values in winter [48,81] Males have higher incidence and much higher CFRs than females Smoking reduces 25(OH)D [82] CFR increases with age Chronic disease rates increase with age; vitamin D plays a role in reducing risk of chronic diseases [83] Higher CFR for diabetics Diabetics may have lower 25(OH)D [84] Higher CFR for diabetics Lower 25(OH)D associated with increased risk of incidence [85] Higher CFR for hypertension Lower 25(OH)D may be associated with increased risk of incidence [86] Higher CFR for cardiovascular disease Lower 25(OH)D associated with increased risk of incidence and death [87] Higher CFR for chronic respiratory disease For COPD patients, 25(OH)D inversely correlated with risk, severity, and exacerbation [88] Found at higher rates in regions with elevated air pollution Air pollution associated with lower 25(OH)D concentrations [89] Note: 25-hydroxyvitamin D ((25(OH)D); acute respiratory distress syndrome (ARDS); community-acquired pneumonia (CAP); case-fatality rate (CFR); interleukin 6 (IL-6); chronic obstructive pulmonary disease (COPD); C-reactive protein (CRP); vitamin D deficiency (VDD). Table 3 lists some findings for vitamin D supplementation in reducing the clinical effects of COVID-19 infection found from treating other diseases.…”

Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

“…Inverse correlation [70], [71] Increased CRP Inverse correlation [72], [73] Increased risk of sepsis Inverse correlation [74], [75] Risk of ARDS Inverse correlation [76], [77] Risk of heart failure Inverse correlation [78], [79] Risk of diabetes mellitus Inverse correlation [80], [67] Epidemiological characteristics Began in December 2019 in China, spread mainly to northern midlatitude countries Low 25(OH)D values in winter [48], [81] Males have higher incidence and much higher CFRs than females Smoking reduces 25(OH)D [82] CFR increases with age Chronic disease rates increase with age; vitamin D plays a role in reducing risk of chronic diseases [83] Higher CFR for diabetics Diabetics may have lower 25(OH)D [84] Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 30 March 2020 doi:10.20944/preprints202003.0235.v2…”

The Role of Micronutrients in Support of the Immune Response against Viral Infections

“…Different factors might explain these geographical variations, such as the earlier spread of the virus in certain countries or the different preventive measures adopted, the different climates and air-pollution levels, or the different age-composition and social proximity of the communities. A North–South gradient in COVID-19 distribution has been noticed [ 174 , 175 , 176 ]. Areas along a latitude of 30–50° N with similar low-humidity, temperate weather, showed significant community spread of COVID-19 [ 177 ].…”