Innate differences in immunity can be detected at
birth, according to new research at Washington University School of Medicine in
St. Louis. And babies with a better innate response to viruses have fewer
respiratory illnesses in the first year of life.
"Viral
respiratory infections are common during childhood," says first
author Kaharu Sumino, MD, assistant professor of medicine. "Usually they
are mild, but there's a wide range of responses — from regular cold symptoms to
severe lung infections and even, in rare instances, death. We wanted to look at
whether the innate immune
response — the response to viruses that you're born with — has any
effect on the risk of getting respiratory infections during the baby's first
year."
Reporting in the May
issue of the Journal of Allergy and Clinical Immunology,Sumino and
her colleagues found that newborns with a diminished immune response to viruses
experienced more respiratory infections in their first year of life than
newborns whose immune response was more robust.
Using umbilical cord
blood samples taken in the delivery room, the researchers measured a specific
immune system response to viral infection known as interferon-gamma
(IFN-gamma). IFN-gamma is released by some cells of the immune system when they
encounter a virus. An important weapon in the immune system's arsenal,
IFN-gamma helps fight viruses by stopping them from replicating.
The researchers studied
cord blood samples from 82 babies in
St. Louis enrolled in the Urban Environment and Childhood Asthma (URECA) trial.
Eighty-five percent of the infants were African-American, and all lived in an
area where at least 20 percent of the residents were below the poverty level.
All had at least one parent with allergies, asthma or eczema, putting them at
higher risk for these conditions themselves.
As reported by their
caregivers, the babies averaged four colds in their first year with 88 percent
of them suffering at least one cold. But the range varied widely with some
caregivers reporting no colds and a few reporting as many as nine or 10.
To measure the innate immune response,
the blood samples were
taken at birth, before any exposure to the environment could influence the
child's immunity. The researchers isolated monocytes, a specific type of white
blood cell, from the babies' cord blood, and infected these cells with a common
respiratory virus.
They then measured the
amount of IFN-gamma produced by the monocytes in response to the virus.
In general, babies whose
monocytes responded to the virus by producing higher levels of IFN-gamma had
fewer reported colds. Likewise, babies whose monocytes produced lower IFN-gamma
levels had more reported colds.
The scientists also found
that newborns whose monocytes produced less IFN-gamma also experienced more ear
infections, sinus infections, pneumonia, and hospitalizations due to
respiratory illness during their first year. But low IFN-gamma levels were not
associated with croup or "stomach flu," indicating that this system
may be closely associated with respiratory viruses and not other types of
infections.
In an effort to identify
other indicators of viral response, the researchers measured amounts of two
other immune molecules: chemokine CCL5 and STAT1. Unlike IFN-gamma, neither showed
any correlation with the number of illnesses the babies experienced.
This study in infants, as
well as research in mice and human cells, supports the idea that dialing up the
body's IFN-gamma signaling system may help protect against viral infection. The
report's senior author Michael J. Holtzman, MD, the Selma and Herman Seldin
Professor of Medicine, is working on drug discovery in this area. Unlike a
vaccine, which protects against a specific virus, a drug that improves the
body's innate immunity could help fight a broad range of viruses, including the
constantly evolving seasonal flu.
"Ideally, if these
results are confirmed, we would like to be able to intervene based on knowledge
of the innate IFN-gamma response," Sumino says. "We're not there yet
— measuring IFN-gamma levels is complex. But in the future, if we can develop a
relatively easy way to find out if someone has a deficiency in this system, we
would like to be able to give a drug that can boost the innate immune response."
More information: Sumino K, Tucker J, Shahab M, Jaffee KF, Visness CM, Gern JE,
Bloomberg GR, Holtzman MJ. Antiviral interferon-gamma responses of monocytes at
birth predict respiratory tract illness in the first year of life. Journal
of Allergy and Clinical Immunology. Vol 129. No 5. May 2012. Online March
29, 2012.
Journal reference: Journal
of Allergy and Clinical Immunology
Provided by Washington
University School of Medicine
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