Vitamin D and innate immunity in pneumonia and COPD

Abstract

A resurgence of interest in vitamin D research has led to the discovery that it plays a role in an unexpectedly large number of biological processes, and that reduced levels of this hormone are implicated in a range of diseases. In fact, it is estimated that vitamin D is involved in the regulation of 3% of the human genome. Two genes containing the target sequence indicative of vitamin D regulation are those encoding LL-37 and hBD-2. These antimicrobial peptides are integral components of the innate immune system and act as natural antibiotics to help combat infection. The respiratory epithelium exposes a large surface area to environmental pathogens, making the innate immune response extremely important in its defence. Microbial infection of the respiratory tract is the cause of pneumonia, and is implicated in cases of COPD exacerbation. This study aimed to determine whether a relationship existed between vitamin D, LL-37 and hBD-2 in 185 patients admitted to Waikato hospital with either condition. It was hypothesised that low vitamin D would correlate with reduced peptide levels, and that this would be associated with increased infection severity and higher mortality rates. Peptide concentrations in patient plasma were measured by indirect ELISA and compared to 25D levels. Statistical analysis revealed no significant associations between vitamin D status, peptide levels and severity, but did show increased mortality in individuals with severe vitamin D deficiency or low LL-37. Based on the significance of LL-37 as a predictor of mortality (particularly in COPD), development of a plasma screening method using MALDI-TOF mass spectrometry was attempted, as a potential means of identifying patients most at risk. The success of this method was limited however, as the low abundance and small size of the mature peptide caused detection problems. A protocol for assessing the vitamin D binding protein (DBP) genotype was developed, as it influences baseline 25D levels and response to supplementation. The association between low vitamin D and mortality suggests that supplementation could improve survival rates and, as the supplement dose required for effectiveness is genotype-dependent, this method could allow determination of the appropriate amount to administer to at-risk individuals.