Introduction:
There is growing evidence that vitamin D is advantageous in preventing and treating a wide range of disorders and that its physiological value extends beyond bone health and calcium homeostasis. Vitamin D has the ability to reduce lung inflammatory reactions while boosting natural defenses against respiratory infections. Randomized controlled clinical trials of vitamin D supplementation in patients with respiratory diseases are strongly justified in light of population-based studies linking circulating vitamin D levels to lung function. These trials will help determine each patient's most effective vitamin D dosage.
What Is Vitamin D?
The biologically active form of vitamin D is 1,25-dihydroxy vitamin D3 [1,25(OH)2D3], which is also known as the "sunshine vitamin" because it is primarily produced from skin-derived precursors by the action of ultraviolet B (UVB) radiation on 7-dehydrocholesterol. Oily fish, fish liver oils, fortified cereals, and dairy products can all be sources of vitamin D in smaller amounts. Through the action of cytochrome P450 enzymes, dietary or synthetic vitamin D from the skin or gut is hydroxylated in the liver to form 25-hydroxyvitamin D [25(OH)D].
Among the over 200 genes that vitamin D controls are those involved in cellular differentiation, death, and proliferation, vitamin D deficiencies are revealing many new roles. The risk of certain autoimmune and infectious disorders and several malignancies is now specifically linked to vitamin D deficiency. According to a recent meta-analysis of randomized controlled studies, vitamin D supplements are also linked to a decline in total mortality rates. In terms of respiratory health, vitamin D deficiency has indeed been linked to an increased risk of tuberculosis and upper respiratory tract infections, as well as a reduction in the forced expiratory volume in one second (FEV1) in asthma and wheezing illnesses.
How Does Vitamin D Act as an Immunomodulator?
Vitamin D is typically recognized for its effects on calcium homeostasis and bone mineralization. However, there is now a lot of research to back up its effects on inflammation and immunity. Research into the potential function of vitamin D in preserving immunological homeostasis and delaying the onset of autoimmune processes has exploded since it was discovered that immune cells have nuclear vitamin D receptors (VDR) and hydroxylase enzymes.
Direct vitamin D inhibition of antigen-presenting cells, which are necessary for the start and maintenance of cell-mediated immune responses, is possible. Both the development of monocytes into dendritic cells and the expression of the co-stimulatory and class II MHC molecules are suppressed. Interleukin (interleukin)-1, interleukin-1, and tumor necrosis factor (TNF)- expression is also suppressed. In addition, vitamin D-induced reduction of interleukin-12 release by dendritic cells significantly impacts the differentiation of T lymphocytes.
What Is the Role of Vitamin D in Alleviation of Respiratory Infections?
1. Tuberculosis
Although it has been known for more than 100 years that exposure to sunlight aids in the treatment of tuberculosis, studies conducted in the 1980s showed that adding vitamin D to monocytes and macrophages that were infected with Mycobacterium tuberculosis resulted in a decrease in the bacterial load. Low serum 25(OH)D levels have been linked to an increased likelihood of having active tuberculosis, according to a recent meta-analysis.
Pathogen-associated molecular patterns (PAMPs), structural proteins that the pathogen expresses and which are recognized by toll-like receptors (TLRs) in the host, enable the immune system to identify invading pathogens such as Mycobacterium tuberculosis. CYP27b1 and vitamin D receptors are upregulated due to PAMPs released by Mycobacterium tuberculosis interacting with the Toll-like receptors/1 dimer on macrophages. Recent research has revealed that the induction of CYP27b1 by interleukin-15 results in the bioconversion of 25(OH)D to 1,25(OH)2D3, activation of the vitamin D receptors, and induction of cathelicidin.
A vitamin D response element is found in the cathelicidin gene, which in humans encodes the antimicrobial peptide LL-37. Therefore, vitamin D binding causes Mycobacterium tuberculosis to be killed by LL-37. It has been discovered that the cathelicidin gene is expressed in respiratory epithelial cells, and it has been demonstrated that vitamin D induces cathelicidin in a variety of cell lines, including bronchial epithelial cells.
2. Influenza and Common Cold
Influenza A virus spreads via airborne droplets and direct touch to create catastrophic outbreaks of respiratory disease in people. It is distinguished by acute neutrophil infiltration and bronchial narrowing. Both the innate and adaptive immune systems are involved in influenza infection. Although vitamin D can prevent macrophages from releasing proinflammatory cytokines, it is important to note that this ability is relevant since antimicrobial peptides can also have antiviral properties. Additionally, viral infection enhances vitamin D activation and cathelicidin synthesis. These antimicrobial peptides can be secreted by epithelial cells in the upper and lower airways as a host defense against infection in addition to immune cells.
3. Chronic Obstructive Pulmonary Disease
Airway constriction is a hallmark of chronic obstructive pulmonary disease. It is a word phrase for two major chronic inflammatory pathologies: emphysema in the alveoli brought on by tissue damage and chronic bronchitis, in which the bronchioles shrink due to excessive mucus production. The third greatest cause of death worldwide is anticipated to be chronic obstructive pulmonary disease, which is characterized by neutrophil and macrophage-induced inflammation that develops over several years.
Acute exacerbations of chronic obstructive pulmonary disease are frequently brought on by bacterial or viral infections. Therefore, vitamin D's capacity to boost cathelicidin expression, as described above, may lessen the pathogen burden and the incidence of these exacerbations. Notably, chronic obstructive pulmonary disease flare-ups are most common during the winter, while serum 25(OH)D levels are low.
Muscle weakness is a significant systemic complication of chronic obstructive pulmonary disease and is linked to an elevated mortality risk. Vitamin D receptors are found in skeletal muscle, which is influenced by vitamin D and affects how well it functions. Vitamin D shortage causes muscle weakness. The vitamin D receptor may substantially impact one of the major problems of chronic obstructive pulmonary disease, as it has recently been discovered that polymorphisms in the vitamin D receptor can affect muscle weakness in healthy people and people with the condition. Therefore, vitamin D has greater potential to enhance the quality of life for those suffering from this condition.
4. Asthma
Inflammatory reactions driven by improper Th (T helper cells) lymphocyte responses of the Th2 phenotype characterize asthma and atopic disorders. Studies demonstrating that vitamin D receptor polymorphisms are an asthma risk factor provide clear evidence that vitamin D plays a function in asthma.
Vitamin D is linked to an increase in interleukin-4 expression and tries to skew the immune response to a Th2 phenotype. In contrast, other researchers have found that vitamin D prevents Th2 cells from secreting interleukin-4 and interferon - when interleukin-12 is present. Therefore, naive T cells in the fetus or newborn may react to vitamin D exposure considerably differently than adult T cells.
Glucocorticoids are the most potent anti-inflammatory medications for many immunological illnesses, including asthma. But for some asthma patients, Glucocorticoid resistance or insensitivity is a severe impediment to efficient therapy and a major source of high medical expenses. Recently, some evidence suggests that giving vitamin D to asthmatic patients who are glucocorticoid-resistant can improve their later responsiveness to Dexamethasone by correcting their impaired CD4+ T cell interleukin-10 response to glucocorticoids. This conclusion encourages the use of vitamin D to combat glucocorticoid resistance in inflammatory disorders such as asthma and a variety of other conditions.
Conclusion:
Acute respiratory infections (ARI) affect many people of all ages, including adults as well as children. The primary factor in mortality and morbidity is respiratory tract infections.
There are not many options for acute respiratory infections treatment or prevention. The cornerstone of pneumonia treatment is the use of antibiotics. Zinc and vitamin A supplements have been investigated to prevent and treat acute respiratory infections in underdeveloped nations. Despite contradicting data, it has been demonstrated that these micronutrient supplements lower acute respiratory infection rates. Despite the paucity of strong proof of efficacy, vitamin C (ascorbic acid) has also been utilized to prevent and treat acute respiratory infections.
Due to its ability to boost immunity, vitamin D may also help prevent acute respiratory infections, according to recent studies. Vitamin D is thought to boost the synthesis of natural antibodies. By causing monocyte differentiation and preventing lymphocyte proliferation, vitamin D is also known to boost immunity. It also suggested that vitamin D increases macrophages' capacity for phagocytosis. Blood vitamin D levels should be kept above 30 ng/l (75 nanomoles/liter).
