Vitamin D may help the body fight influenza by controlling inflammation and the amount of virus in the lungs, according to a study in mice led by researchers at Penn State.
The study, published in the journal Frontiers in Immunology, focused on the role of vitamin D receptors, or VDR, and parathyroid hormone in fighting infections with H1N1, a subtype of influenza A. The team found that mice without vitamin D receptors - meaning they could not utilize the vitamin - experienced 21% mortality and more severe symptoms along with clearing the virus slower compared to normal mice.
The stronger symptoms included increased immune cells and signaling in the lungs, which can contribute to more inflammation and damage.
"It appears as though vitamin D is important for helping the immune system return to normal after an influenza infection," said Margherita Cantorna, distinguished professor of molecular immunology at Penn State and senior author on the study. "If the immune system stays in overdrive, it increases inflammation levels higher and higher, which can result in more damage to the lungs."
Cantorna noted that the study was a preliminary study in mice, so more research is needed to better understand if the association remains in humans.
"Vitamin D is stored in fatty tissue and can build up over time, potentially leading to dangerously high levels of calcium in the blood," she explained. "So, while healthy levels of the vitamin may be important to immune responses, we do not currently recommend that people take more vitamin D supplements if they come down with the flu."
For the study, the researchers analyzed the immune responses to H1N1 in mice without vitamin D receptors and in mice that had vitamin D receptors but were treated with high levels of parathyroid hormone, a hormone that helps regulate calcium levels.
"When mice don't have vitamin D receptors, they end up having really high levels of parathyroid hormone as the body tries to compensate for the vitamin deficiency," Cantorna explained. "So, there could be this question of whether the lack of vitamin D causes a different immune response or if it's the high level of this hormone. Having both mouse models helps disentangle those effects."
The researchers also studied mice lacking VDR specifically in myeloid cells, a group of immune cells that includes macrophages and other cells involved in early immune responses to H1N1 infection. This group of mice did not have vitamin D receptors in their myeloid cells but did have the receptors elsewhere in the body.
Comparing all of these models against normal mice as a control allowed the team to separately assess the effect of vitamin D and parathyroid hormone on host resistance to influenza, the researchers said.
All three models had more severe symptoms, more viral load and stronger inflammation than the control group. According to the researchers, this suggests that the receptors, the parathyroid hormone levels and the vitamin D receptor expression in myeloid cells are all individually linked with worse outcomes from influenza.
Mengzhu Tang, graduate student in pathobiology at Penn State and lead author on the paper, said the findings point to potential translational applications for people with vitamin D deficiencies.
"When vitamin D levels are too low, the body creates more parathyroid hormone to help normalize calcium levels in the blood," she said. "Correcting vitamin D deficiency regulates host immunity and normalizes parathyroid hormone levels."
The researchers said that in the future, additional studies are needed to fully understand the role of vitamin D in immune function in humans. For example, research could continue to dissect how myeloid cells are controlled by vitamin D or what other diseases or conditions might benefit from this type of study.
Veronika C. Weaver, research technologist at Penn State; Gustavo A. Nader, professor of kinesiology at Penn State; Nicole E. Froelich, postdoctoral fellow at the Children's Hospital of Philadelphia; Nicholas J. Hanna, doctoral student at West Virginia University; and Troy C. Sutton, principal scientist at the University of Saskatchewan, also co-authored the study.
This work was supported by the National Institutes of Health's National Center for Complementary and Integrative Health under grant number R01AT005378, National Institute of Arthritis and Musculoskeletal and Skin Diseases under grant number R01AR078430, National Institute of General Medical Sciences under grant number T32GM154124, and National Institute of Diabetes and Digestive and Kidney Diseases under grant number T32DK120509; and the U.S. Department of Agriculture's National Institute of Food and Agriculture and Hatch Appropriations under project number PEN04963 and accession number 7006576. This content is solely the responsibility of the authors and does not necessarily reflect the views of the funders.
