LONDON – A detailed understanding of how common cold viruses cause asthma attacks could result in new preventive therapies for asthma, delivered by regular injections, a new study suggests.

The treatment would rely on blocking the action of a cytokine (chemical messenger) called interleukin-25 (IL-25), using a monoclonal antibody. The research, carried out by a team based in the UK, also resolves a long-standing mystery about the unusual type of immune response that occurs when someone with asthma develops a cold, which precipitates an exacerbation of the condition.

Sebastian Johnston, professor of respiratory medicine and allergy at the National Heart and Lung Institute at Imperial College, London, told BioWorld Today: "This study suggests that it is well worth investigating therapy with monoclonal antibodies directed at IL-25 or its receptor. Once this type of antibody is available, it needs to be tested in a viral challenge study in humans, to see if it ameliorates the symptoms of a severe asthma attack."

Johnston and his colleagues reported their findings in the Oct. 1, 2014, issue of Science Translational Medicine in a paper, titled "Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation."

Commenting on the paper, Nathan Bartlett, honorary lecturer at the National Heart and Lung Institute and joint lead author of the study, said: "Our research has shown for the first time that the cells that line the airways of asthmatics are more prone to producing 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."

According to the World Health Organization, 235 million people worldwide suffer from asthma. Many of those experience exacerbations (asthma attacks), which are commonly triggered by respiratory viruses, especially rhinoviruses, the main cause of the common cold.

During an asthma attack, the airways become inflamed and obstructed, with increased mucus production. Many studies have shown that those symptoms are associated with an immune response known as the TH2 response, characterized by the presence of particular immune cells and chemical messengers, which is usually seen in response to allergies and parasitic infections.

By contrast, the TH1 response involves cells and chemical messengers more commonly present during viral infections. As the TH1 response represses the TH2 response and vice versa, immunologists have been at a loss to explain why the TH2 response is present in an asthma attack caused by a viral infection.

When considering how to find out why the TH2 response is important in the development of an asthma attack, Johnston, Bartlett and their team turned their attention to IL-25 for several reasons. First, it was known to initiate and regulate the TH2 immune response. In addition, several earlier studies had suggested that IL-25 might play a role in asthma. For example, in one study using a mouse model of allergic airway disease, blocking IL-25 reduced the level of allergic inflammation following challenge with an allergen. Other researchers had also reported that infection with respiratory syncytial virus induced IL-25 in the lungs of mice, begging the question of whether infection with the more common rhinovirus might do the same.

Furthermore, IL-25 is expressed by the same airway cells that rhinovirus infects and is known to induce a whole range of TH2 cytokines, including IL-5 and IL-13 – other recent studies had shown that blocking IL-5 and IL-13 could reduce the frequency with which asthma attacks recur.

Johnston, Bartlett and their colleagues therefore came up with the hypothesis that infection with rhinoviruses could induce IL-25 production, leading to TH2 immune responses and inflammation of the airways during asthma attacks triggered by rhinoviruses.

For their study, they compared cells taken from the lungs of people with asthma with those from healthy volunteers. They found that, when they infected the cells with rhinovirus, lung cells from people with asthma produced 10 times more IL-25 than those from the healthy people.

Further experiments showed that, when researchers infected both healthy volunteers and people with asthma with rhinovirus, the nasal secretions of those with asthma had a higher level of IL-25. Using a mouse model of asthma, they infected the animals with rhinovirus and established that the raised levels of IL-25 were associated with increased levels of other cytokines involved in the TH2 response.

Finally, when they blocked IL-25 in the mouse model of asthma infected with rhinovirus, they found that levels of those other TH2-type cytokines also fell.

"In our study, we used an antibody to block the IL-25 receptor, and this successfully blocked the increased TH2 response caused by rhinovirus infection," Johnston said. "There are already plenty of therapies that use monoclonal antibodies so it wouldn't be challenging to develop a human monoclonal antibody to target either IL-25 itself or the IL-25 receptor."

That type of therapy would need to be given by injection, but two or three injections over the course of a winter would probably suffice, he said.

"Alternatively, it might be possible to develop a small molecule that could target IL-25," he added. "This would be a little more challenging to achieve but could be given orally."

The team currently is investigating what other cytokines are produced during viral-induced asthma attacks.

"We have found that IL-33 is also produced by epithelial cells, and that it, too, directly induces TH2 responses. This could be another potential target for therapy," Johnston said. "We would like to understand whether IL-25 or IL-33 is a better target."