Endocrine, Metabolic & Immune Disorders-Drug Targets Vol 14, issue 4, Pages 255-266 (12)
Chunxiao Guo and Adrian F. Gombart
Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, USA.
The recent discovery that vitamin D regulates expression of the cathelicidin antimicrobial peptide gene has generated renewed interest in using vitamin D to fight infectious diseases. This review describes the historical use of vitamin D or its sources to treat infections, the mechanism of action through which vitamin D mediates its “antibiotic” effects, findings from epidemiological studies associating vitamin D deficiency with increased susceptibility to infection and clinical trials with vitamin D supplementation to treat or prevent infections. Furthermore studies examining an association between vitamin D levels and cathelicidin expression are discussed. The role of cathelcidin throughout the course of infection from the initial encounter of the pathogen to the resolution of tissue damage and inflammation indicates that individuals need to maintain adequate levels of vitamin D for an optimal immune response. In addition, for treating infections, carefully designed randomized, clinical trials that are appropriately powered to detect modest effects, target populations that are severely deficient in vitamin D, and optimized dose, dosing frequency and safety are needed.
In vitro studies of the past 30 years have identified numerous mechanisms for the antibiotic effects of vitamin D in humans with induction of antimicrobial or bactericidal peptides being of greatest interest.
In addition, historically, sources of vitamin D have shown efficacy in treating infectious diseases primarily pulmonary and cutaneous (lupus vulgaris) mycobacterium tuberculosis infections.
The improvement of lupus vulgaris patients with very high dose vitamin D therapy was quite striking. More recent studies with pulmonary tuberculosis use much lower doses of vitamin D in combination with current antibiotic therapies and the findings are mixed. Studies with other infectious conditions suggest that adequate vitamin D levels or supplementation with vitamin D may be important in reducing respiratory tract and vaginal infections. Again, other studies have shown no benefit, thus researchers need to carefully design future studies that are well-controlled, randomized, clinical trials that are appropriately powered to detect modest effects. Also, investigators need to target populations that are severely deficient in vitamin D, optimize the dose, dosing frequency and safety. While direct killing of pathogens by cathelicidin may explain, in part, the antibiotic properties of vitamin D, the activation of various transmembrane receptors, dampening of TLR signaling and induction of autophagy mediated by this peptide need to be explored more fully to understand how vitamin D functions in modulating the immune response. Because the cathelicidin peptide combats infection at all stages from the initial response of killing microbes and inhibiting biofilms to resolution through recruitment of other immune cells and healing by promoting angiogenesis and migration of epithelial cells in wound healing, it is important for individuals to maintain adequate levels of vitamin D for an optimal immune response.
- Overview Tuberculosis and Vitamin D
- Lupus category listing with associated searches
- Lupus reduced with vitamin D intervention – Feb 2014
- Acute respiratory infection treated by vitamin D in 6 of 12 clinical trials – review Nov 2012
- Search VitaminDWiki for cathelicidin 345 hits as of Nov 2014
see also Search RTI OR "Respiratory Tract Infection" 177 items as of July 2014