Journal of Clinical Investigation 2005, 8 December 2005
Asthma patients who don't respond to steroid treatment suffer repeated asthma attacks, and are at greater risk of dying from the condition. Researchers from King's College London have found that vitamin D3 could substantially improve the responsiveness of these patients to steroid treatment, offering them hope of an improvement in their condition. Their results are published today in the Journal of Clinical Investigation.
Asthma is usually treated very effectively with inhaled steroids but for some patients, taking steroid tablets is the only way of controlling their condition, and this can cause considerable side effects. Unfortunately a sub-group of people with severe asthma fail to show clinical improvement, even with high doses of oral steroids, limiting their treatment options.
Professor Tak Lee, Director of the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma at King's College London and Imperial College, who was involved in the latest study, explained its importance: 'This research is really exciting and points the direction towards potential new strategies for reversing steroid resistance. This has major implications for how to treat patients with severe asthma and could also substantially reduce the use of NHS resources.'
The team's results imply that steroid treatment works, at least in part, by inducing the T-cells of the immune system to synthesise a secreted signalling molecule, called IL-10. This molecule can inhibit the immune responses that cause the symptoms of allergic and asthmatic disease.
Unlike T-cells from healthy individuals, or patients that respond to steroids, T-cells taken from patients who are steroid resistant do not produce IL-10 when cultured in vitro with the steroid, dexamethasone.
However, the researchers found that when vitamin D3 was added to the culture medium along with dexamethasone, this defect was reversed and the previously steroid-resistant cells were able to respond to the treatment by producing IL-10 to the same extent as T-cells taken from steroid-responsive patients.
Adding vitamin D3 to cultures of T-cells from healthy individuals or from steroid-responsive patients made these cells even more responsive to steroids than before.
Dr Catherine Hawrylowicz, who led the King's research team said: 'The hope is that this work will lead to new ways to treat people who don't respond to steroid treatment as it currently stands, and it could also help those people who are on heavy doses of steroids to reduce the amount of medication they are taking.'
To test whether this therapy could work in practice the team at King's went on to perform a pilot experiment where people with asthma who were unresponsive to steroids took daily vitamin D3 supplements for seven days. The researchers took blood samples to assess whether the patients' T-cells were more responsive to dexamethasone after they had taken the supplement. The test results were positive.
Dr Hawrylowicz said: 'This is a great example of how productive basic science collaborations can translate into studies in patients. Our research began more than five years ago with Dr Anne O'Garra from the MRC National Institute for Medical Research at Mill Hill.'
She added: 'At the moment we only have a preliminary experimental observation, that ingestion of vitamin D3 can increase the responsiveness of T-cells from patients with steroid-resistant asthma to steroids. We now need to test the benefits of this treatment in the clinic, and we are currently putting a proposal together to carry out this work.
'Interestingly, vitamin D3 is at present occasionally administered to patients with severe asthma to help prevent steroid-induced osteoporosis. Our studies suggest that there is an additional potential benefit to this treatment.'
Dr. Lyn Smurthwaite, Research Development Manager at Asthma UK said: '2.6 million people in the UK have severe asthma symptoms, many of whom have restricted treatment options available to them as they do not respond to conventional steroid therapy. Asthma UK is very pleased to have funded this research which opens up a potentially important new avenue for developing treatments for people with difficult to control asthma.'