New therapeutic targets for virally-induced asthma attacks suggested

May 29, 2011

When children with asthma get the flu, they often land in the hospital gasping for air. Researchers at Children's Hospital Boston have found a previously unknown biological pathway explaining why influenza induces asthma attacks. Studies in a mouse model, published online May 29 by the journal Nature Immunology, reveal that influenza activates a newly recognized group of immune cells called natural helper cells – presenting a completely new set of drug targets for asthma.

If activation of these cells, or their asthma-inducing secretions, could be blocked, asthmatic children could be more effectively protected when they get the and possibly other viral infections, says senior investigator Dale Umetsu, MD, PhD, of Children's Division of Immunology.

Although most asthma is allergic in nature, attacks triggered by viral infection tend to be what put children in the hospital, reflecting the fact that this type of asthma isn't well controlled by existing drugs.

"Virtually 100 percent of asthmatics get worse with a viral infection," says Umetsu. "We really didn't know how that happened, but now we have an explanation, at least for ."

Natural helper cells were first, very recently, discovered in the intestines and are recognized to play a role in fighting parasitic worm infections as part of the innate immune system (our first line of immune defense).

"Since the lung is related to the gut – both are exposed to the environment – we asked if natural helper cells might also be in the lung and be important in asthma," Umetsu says.

Subsequent experiments, led by first authors Ya-Jen Chang, PhD, and Hye Young Kim, PhD, in Umetsu's lab, showed that the cells are indeed in the lung in a of influenza-induced asthma, but not in allergic asthma. The model showed that influenza A infection stimulates production of a compound called IL-33 that activates natural helper cells, which then secrete asthma-inducing compounds.

"Without these cells being activated, infection did not cause airway hyperreactivity, the cardinal feature of asthma," Umetsu says. "Now we can start to think of this as a target – IL-33, the natural helper cell itself or the factors it produces."

Personalized medicine in asthma?

The study adds to a growing understanding of asthma as a collection of different processes, all causing airways to become twitchy and constricted. "In mouse models we're finding very distinct pathways," Umetsu says.

Most asthma-control drugs, such as inhaled corticosteroids, act on the best-known pathway, which involves known as TH2 cells, and which is important in allergic asthma. However, Umetsu's team showed in 2006 that a second group of cells, known as natural killer T-cells (NKT cells), are also important in asthma, and demonstrated their presence in the lungs of asthma patients. NKT cells, they showed, can function independently of TH2 cells, for example, when asthma is induced with ozone, a major component of air pollution. Compounds targeting NKT are now in preclinical development.

The recognition now of a third pathway for asthma, involving natural , may reflect the diversity of triggers for asthma seen in patients.

"Clinically, we knew there were different asthma triggers, but we thought there was only one pathway for asthma," Umetsu says, adding that all of the identified pathways can coexist in one person. "We need to understand the specific asthma pathways present in each individual with and when they are triggered, so we can give the right treatment at the right time."

Related Stories

Recommended for you

Antibody found that fight MERS coronavirus

July 28, 2015

(Medical Xpress)—An international team of researchers has found a MERS neutralizing antibody—a discovery that could perhaps lead to a treatment for people infected with the virus. In their paper published in Proceedings ...

Experimental MERS vaccine shows promise in animal studies

July 28, 2015

A two-step regimen of experimental vaccines against Middle East respiratory syndrome (MERS) prompted immune responses in mice and rhesus macaques, report National Institutes of Health scientists who designed the vaccines. ...

Can social isolation fuel epidemics?

July 21, 2015

Conventional wisdom has it that the more people stay within their own social groups and avoid others, the less likely it is small disease outbreaks turn into full-blown epidemics. But the conventional wisdom is wrong, according ...

Lack of knowledge on animal disease leaves humans at risk

July 20, 2015

Researchers from the University of Sydney have painted the most detailed picture to date of major infectious diseases shared between wildlife and livestock, and found a huge gap in knowledge about diseases which could spread ...

IBD genetically similar in Europeans and non-Europeans

July 20, 2015

The first genetic study of inflammatory bowel disease (IBD) to include individuals from diverse populations has shown that the regions of the genome underlying the disease are consistent around the world. This study, conducted ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.