Immunoregulation of Inflammatory and Inhibitory Cytokines by VitaminD3 in Patients with Inflammatory Bowel Diseases

Abstract

Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of vitamin D3 in patients with IBD exerts both direct and indirect regulatory roles on the na€ ıve T cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of vitamin D3 on na€ ıve T cells result in the proliferation of more regulatory T cells and inhibitory cytokines such as IL-4, IL-10 and IL-5. The binding of vitamin D to dendritic cells (DCs) through vitamin D receptors inhibits the action of IL-12 on DCs, resulting in the downregulation of Th1 and Th17. On the other hand, this interaction favours Th2 and Treg upregulation and facilitates the maintenance of immune homoeostasis between inflammatory and inhibitory cytokines which is essentially significant in the management of patients with IBD. The aim of this review was to explore the current and mounting scientific evidence on the roles of vitamin D3 in immunoregulation of inflammatory and inhibitory cytokines in patients with IBDs. An extensive literature search was conducted using keywords such as Vitamin D3*, IBD*, inflammatory cytokines*, inhibitory cytokines*, na€ ıve-T-cells* and antigen presenting cells* through PubMed, SCOPUS and MEDLINE search engines. The results of the accumulated bodies of research that have been conducted demonstrate that vitamin D3 plays a major role not only in the immunoregulation of cytokines involved in the pathogenesis of IBDs but also in many other inflammatory disorders.

Vitamin D: Nutrient, Hormone, and Immunomodulator

“…In these two conditions 1,25(OH) 2 D 3 prevents the initiation and reduces the disease progression [ 91 , 92 , 93 ]. Similarly, different mouse models of enterocolitis display a more severe phenotype during vitamin D deficiency and reduced inflammation after administration of 1,25(OH) 2 D 3 (see for a review Alhassan et al, 2017) [ 94 ]. Despite solid experimental evidence human studies are less convincing: some epidemiological data link increasing latitude and consequent decrease sunlight exposure with higher prevalence of multiple sclerosis [ 95 , 96 , 97 ], type I diabetes [ 98 , 99 , 100 ], and IBD [ 101 ].…”

Diet supporting therapy for inflammatory bowel diseases

“…Vitamin D affects also an epithelial integrity in a process of inhibiting intestine epithelial apoptosis, by which influences intestinal inflammation and healing process. Vitamin D increases the suppressive mediators of inflammation production such as IL-4, IL-5 and IL-10, but reduces IL-12, IFN-γ, IL-2, IL-17, TNF-α concentrations that are responsible for stimulating inflammation [ 43 ].…”

Inflammatory bowel disease and immunonutrition: novel therapeutic approaches through modulation of diet and the gut microbiome

“…Besides its actions on the gut microbiota, vitamin D also impacts host immunity, including immune cell differentiation, migration and anti‐inflammatory functions. The immunomodulatory effects of vitamin D supplementation in patients with IBD are reviewed by Mohammed et al . Human monocytes and macrophages treated with vitamin D show enhanced antimicrobial ability through improved autophagy and increased production of antimicrobial peptides, while also exhibiting reduced TLR‐mediated inflammatory responses upon recognition of microbial products .…”