Heightened Immunity To Colds Makes Asthma Flare-Ups Worse, U-M Research Shows

Tempering the immune response — rather than enhancing it — in asthma patients might be a better strategy when combating cold symptoms

People often talk about “boosting” their immunity to prevent and fight colds. Nutritional supplements, cold remedies and fortified foods claim to stave off colds by augmenting the immune system.

A new University of Michigan study shows this strategy might actually be flawed. The results may hold important implications for individuals with asthma, who often experience life-threatening flare-ups due to infections with cold viruses.

The study, using a novel mouse model, shows that, in the airways, the immune response to the common cold is actually maladaptive. Mice that were engineered to have a reduced innate immune response to the common cold actually showed less – not more – airway inflammation and bronchoconstriction (airway spasm) following infection.

The results of this study appeared online ahead of print in the journal PLoS Pathogens, currently available online. Marc B. Hershenson, M.D., professor of pediatrics and communicable diseases and director of the division of pediatric pulmonology, is the study’s senior author.

“You often hear that people want to boost their immunity to prevent and fight colds,” says Hershenson. “However, boosting the immune response could increase inflammation. Up to now there have been no convincing data supporting the theory that the immune response might be deleterious. In our study, we offer the first direct evidence that limiting the immune response reduces the manifestations of rhinovirus infection.”

“In our model, cold-induced asthma flare-ups were caused by the body’s immune response to the virus, not the virus itself. Chemicals produced by the immune system inflame cells and tissues, causing asthma symptoms such as cough and wheeze,” Hershenson explained.

Hershenson and his group hypothesized that limiting the immune response to viral infection would actually reduce their symptoms. Using a rhinovirus 1B, a cold virus strain that replicates in mouse lungs, they infected mice deficient in MDA5 and TLR3 – two receptors that trigger the protective defenses of the immune system against viruses and other pathogens.

MDA5-deficient mice showed a delayed defensive response to the infection, leading to a small increase in the level of virus in the lungs. Nevertheless, these mice showed less airway inflammation and bronchoconstriction following infection compared to wild-type mice. TLR3-deficient mice also showed diminished airway responses.

In addition, MDA5- and TLR3-null mice that were made asthmatic by exposure to allergen showed decreased airway inflammatory and contractile responses in response to rhinovirus infection compared to normal mice. These results suggest that, in the context of rhinovirus infection, reducing the mouse’s innate immune system led to reduced inflammatory signaling pathways and reduced airways inflammation and hyper-responsiveness.

“This study shows that, once you have a cold, elements of the immune response actually make the symptoms worse,” Hershenson adds. “A better strategy might be to modulate the immune response in asthma patients with colds.”

Contacts and sources:

Written by Margarita Wagerson

University of Michigan Health System

Authors: Qiong Wang, Ph.D., David J. Miller, M.D., Ph.D., Emily R. Bowman, Deepti R. Nagarkar, Ph.D., Dina Schneider, Ph.D., Ying Zhao, Marisa J. Linn, Adam M. Goldsmith, Ph.D., J. Kelley Bentley, Ph.D., Umadevi S. Sajjan, Ph.D, Marc B. Hershenson, M.D., all of the University of Michigan

Funding: National Institutes of Health

Disclosures: None

Citation: Wang Q, Miller DJ, Bowman ER, Nagarkar DR, Schneider D, et al. (2011) MDA5 and TLR3 Initiate Pro-Inflammatory Signaling Pathways Leading to Rhinovirus-Induced Airways Inflammation and Hyperresponsiveness. PLoS Pathog 7(5): e1002070. doi:10.1371/journal.ppat.1002070

The University of Michigan C.S. Mott Children’s Hospital is consistently ranked as one of the best hospitals in the country. It was nationally ranked in all ten pediatric specialties in the U.S. News Media Group’s 2011 edition of “America’s Best Children’s Hospitals” including third in the country for heart and heart surgery. In November, the hospital moves to a new 1.1 million square feet, $ 754 million state-of-the-art facility that will be home to cutting-edge specialty services for newborns, children and women.

Study shows connection: asthma, early vaccinations

From the Canadian Press, important but probably something you won’t see written up in the US media venues.

U of M researcher links asthma, early vaccinations
By Jen Skerritt Thursday, January 24th, 2008

Children who have their routine vaccinations delayed by two months or more cut their risk of asthma by half, a University of Manitoba researcher has found.

Anita Kozyrskyj, an asthma researcher in the U of M faculty of pharmacy, studied the immunization and health records of 14,000 children born in Manitoba in 1995.

Kozyrskyj found nearly 14 per cent of the children who received their first shot of diphtheria, pertussis, tetanus vaccine at two months of age developed asthma — compared with only 5.9 per cent of children who were vaccinated more than four months after the scheduled date.

Manitoba recommends vaccinating children at two months, four months, six months and 18 months of age for diphtheria, pertussis (whooping cough) and tetanus (DPT).

The DPT causes an allergic reaction and Kozyrskyj said researchers are speculating whether children’s immune systems are better able to handle the vaccine’s side effects when they’re older. The pertussis vaccine used in Manitoba before 1997 caused fever in some children, and some studies have linked fever in early childhood to a greater risk of developing asthma.

The study’s findings are going to be published in the U.S. Journal of Allergy and Clinical Immunology within the next few weeks.

“We’re thinking that maybe if you delay this allergic response until a bit later, the child’s immune system is more developed and maybe you’re not seeing this effect,” Kozyrskyj said.

The findings come as little surprise to parents who have spoken out against the risks of vaccinating infants at an early age.

The prevalence of childhood disorders like asthma and auto-immune disorders like autism has increased over the last few decades, leaving many parents wondering whether childhood vaccinations may be contributing to the rise.

“They’re barely out of the protection of the womb before we’re sticking vaccines in them,” said Irene Gergus, a Winnipeg mom whose son Andrew lost his ability to speak shortly after receiving his fourth DPT shot at 18 months in 1993.

“I’m not against vaccination I just think they’re too young to be receiving (them).”

Kozyrskyj is the first researcher to study the effect between asthma and vaccines, but said she doesn’t believe the findings will spur a change the province’s vaccination schedule. She said Japan recommended children under 10 months not be vaccinated between 1975 and 1988, and the country saw a spike in the number of childhood cases of whooping cough.

Kozyrskyj said she is “pro-vaccination” and noted the safety and efficacy of vaccines has been studied for years.

“It’s not an alarm bell,” she said. “We have many years of research on these vaccines and I would say the benefits, by far, outweigh the risks.”

Of the 14,000 immunization records Kozyrskyj studied, 11,531 children received at least four doses of DPT.

Overall, nearly 12 per cent of the children who received at least four doses of DPT had asthma. The majority of children who had asthma lived in urban areas and were predominantly male.

Kozyrskyj said researchers did not compare the risk of asthma among children who did not receive any vaccinations, saying only about 100 children in the province did not receive DPT — a number that would not be statistically significant.

jen.skerritt@freepress.mb.ca
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