and Medicine for Seniors
Old Lungs Look
New Again - Ibuprofen Reduces Inflammation in Elderly
someday support use of ibuprofen as adjunct therapy for senior citizens
2, 2014 - New research shows that the lungs become more inflammatory
from cell damage with age and that ibuprofen can lower that
inflammation. Researchers have found that immune cells from old mouse
lungs fought tuberculosis bacteria as effectively as cells from young
mice after lung inflammation was reduced by ibuprofen.
research establishing inflammation’s links to aging and disease has
tested blood for elevated proteins that signal an inflammatory
environment. These researchers found the same proteins in the lungs of
old mice. Research has already established that the inevitable
inflammation that comes with aging is linked to such conditions as Type
2 diabetes and heart disease.
This was a rare
look at inflammation in the aging lung environment by
University scientists who study the immune response to
tuberculosis (TB). The researchers already knew that old mice had a
harder time clearing TB from the lungs than young mice, but had not
investigated the role of lung inflammation in that response.
ibuprofen had no effect on the immune response to TB in young mice.
researchers have linked inflammation to infectious disease in old age,
even though TB in particular will drive that inflammation even further,”
associate professor of
infection and immunity at Ohio State and senior author of the
inflammation-associated changes that we saw in the lung were a small
finding, but an important finding because the implications are great,”
Turner said. “We should be able to modify the environment in the lung.
If we can reverse the inflammatory environment in a very straightforward
way that is a positive.”
The research is
published in the
Though this line
of work might someday support the use of ibuprofen as an adjunct therapy
for elderly people with TB, Turner emphasized that she and colleagues
are not recommending use of the drug for the purposes of lowering
actually reduce your inflammation as you age by being lean, eating well
and exercising. And we know that in the elderly, people who are fitter
live longer,” she said. “Inflammation is associated with sickness and
research was conducted in mice, Turner co-led a previous study
indicating that both mouse and human lungs develop the same profile of
pro-inflammatory proteins and fatty molecules with age, creating an
environment that impairs the immune response to infection.
More than 9
million people worldwide are estimated to have active TB infections, and
about 1.4 million people die of tuberculosis each year.
“The elderly are
most likely to die of TB. They get sicker. They’re not the biggest
population that gets infected with TB, but they can develop the worst
cases,” said Turner, also an associate director of Ohio State’s
Microbial Interface Biology (CMIB).
In this new
study, the researchers compared lung cells from old and young mice and
found that in the old mice, genes that make three classic
pro-inflammatory proteins, called
were more active in the lungs of old mice. The cytokines are
immune system cells called
in the lungs from old mice were in an advanced state of readiness to
fight an infection – a status that signals inflammation. Macrophages in
young mouse lungs were in a normal, resting state.
In test tubes,
the scientists exposed mouse lung macrophages to TB bacteria. The
macrophages from old mouse lungs were quicker to absorb the bacteria
than were immune cells from young mice, but that initial robust immune
response from the cells of old mice could not be sustained.
macrophage in an old mouse has lots of receptors on its surface that can
bind to TB, taking it up and trying to kill it. But what it lacks is the
ability to increase the response further,” Turner said. “A resting
macrophage in a young mouse takes up TB and then can be activated to do
something even more effective at killing the bacteria.”
elements of the elderly response to TB remain a mystery, this finding
suggested that the inflammation in the lungs of elderly mice had the
direct effect of reducing the long-term effectiveness of their immune
response to TB infection, Turner said.
Old mice in the
study were 18 months old – equivalent to about 65 in human years – and
young mice were 3 months old, a similar age to human young adults.
gave old and young mice ibuprofen in their food for two weeks and then
examined their lung cells. After this diet modification, several
pro-inflammatory cytokines in the lungs of old mice had been reduced to
levels identical to those in the lungs of young mice, and the
macrophages in old mouse lungs were no longer in a primed state.
“There’s a trend
toward reduced inflammation. Essentially, ibuprofen made the lungs of
old mice look young. Putting young mice on ibuprofen had no effect
because they had no lung inflammation, which implies the ibuprofen
reduced the inflammation and changed the immune response in the old
mice,” Turner said.
“It might be
that ibuprofen works on specific pathways to lower inflammation, and
that might help with control of TB.”
colleagues have extended the work to test whether ibuprofen affects the
elderly mouse immune response to TB infection.
This work was
supported by a Julie Martin Mid-Career Award from the
Federation for Aging Research, the
University Public Health Preparedness for Infectious Diseases Pilot
Award and Ohio State’s
Medicine Systems and Integrative Biology Training Program.
include Cynthia Canan, Nandan Gokhale (now at Duke University), Bridget
Carruthers (now with Ohio State’s Office of Environmental Health and
Safety), William Lafuse, Larry Schlesinger and Jordi Torrelles, all of
Ohio State’s Department of Microbial Infection and Immunity and CMIB.