Vitamin D effects on lung immunity and respiratory diseases

Abstract

Our understanding of vitamin D metabolism and biological effects has grown exponentially in recent years and it has become clear that vitamin D has extensive immunomodulatory effects. The active vitamin D generating enzyme, 1α-hydroxylase, is expressed by the airway epithelium, alveolar macrophages, dendritic cells, and lymphocytes indicating that active vitamin D can be produced locally within the lungs. Vitamin D generated in tissues is responsible for many of the immunomodulatory actions of vitamin D. The effects of vitamin D within the lungs include increased secretion of the antimicrobial peptide cathelicidin, decreased chemokine production, inhibition of dendritic cell activation, and alteration of T-cell activation. These cellular effects are important for host responses against infection and the development of allergic lung diseases like asthma. Epidemiological studies do suggest that vitamin D deficiency predisposes to viral respiratory tract infections and mycobacterial infections and that vitamin D may play a role in the development and treatment of asthma. Randomized, placebo-controlled trials are lacking but ongoing.

Figure 1. Epidemiological associations between vitamin D deficiency and lung diseases and proposed mechanisms

Vitamin D deficiency appears to increase susceptibility to TB infections due to lack of induction of the cathelicidin antimicrobial peptide. Vitamin D deficient individuals also report more frequent respiratory tract infections perhaps due to less production of cathelicidin and/or increased production of chemokines leading to uncontrolled inflammatory response. Lastly vitamin D deficiency has been associated with higher prevalence of asthma and a more severe course of this disease. Two mechanisms have been proposed: i) Increased risk of respiratory viral infection. ii) Lack of vitamin D suppressive effects on adaptive immunity, in particular dendritic cells and T regulatory cells.