MAKING OLD LUNGS LOOK YOUNG AGAIN WITH IBUPROFEN
New research shows
that the lungs become more inflammatory with age and that ibuprofen can lower
that inflammation
In fact, immune cells
from old mouse lungs fought tuberculosis bacteria as effectively as cells from
young mice after lung inflammation was reduced by ibuprofen. The ibuprofen had
no effect on the immune response to TB in young mice.
This was a rare look
at inflammation in the aging lung environment by Ohio State University
scientists who study the immune response to 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.
"Very few
researchers have linked inflammation to infectious disease in old age, even
though TB in particular will drive that inflammation even further," said
Joanne Turner, associate professor of microbial infection and immunity at Ohio
State and senior author of the study.
"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 Journal of Leukocyte Biology.
Most previous 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.
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 inflammation.
"You can 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 frailty."
Though the 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 Center for 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
cytokines, were more active in the lungs of old mice. The cytokines are
interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha
(TNF-a). In addition, immune system cells called macrophages 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.
"A primed
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."
Though some 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.
The researchers 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."
Turner and colleagues
have extended the work to test whether ibuprofen affects the elderly mouse
immune response to TB infection.
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