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.
"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.
Story
Source:
The above story is based on materials provided by Ohio State University. The original
article was written by Emily Caldwell. Note:
Materials may be edited for content and length.
Journal
Reference:
C. H. Canan, N. S. Gokhale, B. Carruthers, W. P. Lafuse, L. S.
Schlesinger, J. B. Torrelles, J. Turner. Characterization
of lung inflammation and its impact on macrophage function in aging. Journal of Leukocyte Biology,
2014; 96 (3): 473 DOI: 10.1189/jlb.4A0214-093RR
Cite
This Page:
Ohio State University. "Making old lungs look young again,
with ibuprofen." Science Daily,
2 October 2014. <www.sciencedaily.com/releases/2014/10/141002100853.htm>.
