Researchers have identified a molecular mechanism that could
explain why the common cold can bring on life-threatening asthma
attacks.
The findings indicate this may be a potential target for new
drugs that could be more effective than existing treatments.
Viruses that infect the airways are the most common cause of
asthma attacks, accounting for 80-90 per cent of cases. The great
majority of these are rhinoviruses, which are the predominant cause
of the common cold.
Although illnesses caused by rhinoviruses are usually relatively
mild for most people, they can also infect the lungs and, in people
with respiratory diseases such as asthma, they can trigger severe
attacks, sometimes leading to hospitalisation. The hallmark
features of an asthma attack are inflammation and obstruction of
the airways, and increased mucus production. These are all part of
type-2 immune responses, which usually occur in response to
allergies and parasitic infections. Until now it has been
unclear how a rhinovirus infection can trigger such a response.
The new study, conducted at the Medical Research Council (MRC)
and Asthma UK Centre in Allergic Mechanisms of Asthma at Imperial
College London and King's College London, has confirmed that a
small molecule or cytokine called IL-25 may play a central role in
the effects of rhinoviruses on asthmatics. For the first time
researchers have identified a possible sequence of biological
events that could trigger these attacks.
The research shows that IL-25 is induced by rhinovirus
infection, and is capable of instigating the production of other
type-2 cytokines, creating a 'cascade' of these molecules which
drives the type-2 immune response. Recent trials report that
antibodies that block individual type-2 cytokines have modest
therapeutic effects. The hope is that if scientists can target and
block IL-25, this will stop the cascade 'higher up' and potentially
produce a much greater therapeutic effect.
Dr Nathan Bartlett, Honorary Lecturer at the National Heart and
Lung Institute, Imperial College London said: "Our research has
shown for the first time that the cells that line the airways of
asthmatics are more prone to producing a small molecule called
IL-25, which then appears to trigger a chain of events that causes
attacks. By targeting this molecule at the top of the cascade, we
could potentially discover a much-needed new treatment to control
this potentially life-threatening reaction in asthma
sufferers."
The research team compared cells taken from the lungs of
asthmatics to cells from healthy volunteers and demonstrated that,
when infected with a rhinovirus, asthmatic lung cells produce
around 10-fold higher levels of IL-25. To examine IL-25 expression
directly in the airways the researchers then infected asthmatic and
healthy volunteers with a rhinovirus and found that asthmatics had
a higher level of IL-25 in nasal secretions.
By simulating asthma in mice and infecting them with a
rhinovirus, the researchers discovered that increased IL-25 is
associated with increased levels of other cytokines in the type-2
response, and that blocking IL-25 with an antibody decreases the
levels of these other cytokines. These results suggest that IL-25
could be a target for possible treatments to prevent asthma
attacks.
Professor Sebastian Johnston, from the National Heart and Lung
Institute at Imperial College London said: "Asthma attacks are
still a huge healthcare problem. Existing medication containing
inhaled steroids, are highly effective at controlling regular
asthma symptoms, but during an attack the symptoms worsen and can
lead to the patient going to hospital.
"This new study provides exciting results about potential ways
to address this big unmet medical need. The next steps are to test
blocking IL-25 in humans, and to investigate other possible
pathways that could be important in asthma attacks and pool this
knowledge to develop effective treatments." Professor Johnston is
also the Director of the MRC & Asthma UK Centre in Allergic
Mechanisms of Asthma and Asthma UK Clinical Chair.
The paper, Rhinovirus-induced
IL-25 in asthma exacerbation drives type 2 immunity and allergic
pulmonary inflammation, is published in Science
Translational Medicine.