Vitamin supplement could help treatment-resistant
asthma
Vitamin supplement could help treatment-resistant
asthmaDecember 09, 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.' King's
College London
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