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.'
Notes for Editors
This press release is based on the following article:
Reversing the defective induction of IL10 secreting T regulatory cells in glucocorticoid-resistant asthma patients.
Emmanuel Xystrakis, Siddarth Kusumakar, Sandra Boswell, Emma Peek, Paul Lavender, Zoe Urry, David F Richards, Tonye Adikibi, Carol Pridgeon, Margaret Dallman, Tuck-Kay Loke, Douglas S Robinson, Franck J Barrat, Anne O'Garra, Tak H Lee, Christopher Corrigan, Catherine M Hawrylowicz
Journal of Clinical Investigation 2005, 8 December 2005
MRC-Asthma UK Centre in Allergic Mechanisms of Asthma
The MRC-Asthma UK Centre in Allergic Mechanisms of Asthma at King's College London and Imperial College London was launched in September 2005 thanks to funding from both the MRC and Asthma UK. The Centre is directed by Professor Tak Lee from King's and Professor Tim Williams from Imperial. It has three main aims: to advance the understanding of allergic mechanisms in order to inform the development of new, effective and targeted treatments; to provide high-quality, basic and clinical research training in allergy and asthma; and to provide quality public information on allergy and asthma in conjunction with stakeholders and partners.
King's College London
King's College London is one of the two oldest and largest colleges of the University of London with over 13,800 undergraduate students and nearly 5,700 postgraduates in nine schools of study. It is a member of the Russell Group: a coalition of the UK's major research-based universities.
The College has had 24 of its subject-areas awarded the highest rating of 5* and 5 for research quality, demonstrating excellence at an international level, and it has recently received an excellent result in its audit by the Quality Assurance Agency. King's is in the top group of UK universities for research earnings, with income from grants and contracts of £100 million, and has an annual turnover of more than £348 million. In 2004 the College was once again awarded an AA- financial credit rating from Standard & Poor's.
Asthma UK
Asthma UK is the charity dedicated to improving the health and well-being of the 5.2 million people in the UK whose lives are affected by asthma. We work together with people with asthma, health professionals and researchers to develop and share expertise to help people increase their understanding and reduce the effect of asthma on their lives.
Medical Research Council
The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC's expenditure of more than £500 million is invested in its 40 Institutes, Units and Centres. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools. Web site at: http://www.mrc.ac.uk
Journal
Journal of Clinical Investigation