Aerosol launches immune response in lungs to wipe out lethal infections

Dec 03, 2007

An inhaled immune system stimulant protects mice against lethal pneumococcal pneumonia and other deadly bacterial, viral and fungal infections of the lungs, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports at a major scientific meeting.

Their findings have implications for protecting immuno-compromised patients against infection and the general public against respiratory epidemics and biological weapons. The research is a featured presentation at the annual meeting of the American Society for Cell Biology Dec. 3 in Washington, D.C.

"This aerosol stimulates an innate immune system response in the lung lining fluid that kills the invading pathogens virtually on contact," says Brenton Scott, Ph.D., post-doctoral fellow in M. D. Anderson's Department of Pulmonary Medicine, and first author of the abstract presented at ASCB. "It also works in mice with suppressed immune systems."

The innate immune system is the body's inflammatory first response to infection or injury. It produces proteins and peptides that act as natural antibiotics to broadly kill invading bacteria, viruses or fungi.

"Pneumonia is a leading cause of death from infection in the United States and a major cause of death among cancer patients and others with suppressed immune systems," says Burton Dickey, M.D., professor and chair of pulmonary medicine and senior author of the research.

Untreated mice exposed to S. pneumoniae, the most common form of bacterial pneumonia, died within days. Mice treated with the Aerosolized Lung Innate Immune Stimulant (ALIIS), developed by the researchers, two hours before exposure had an 83 percent survival rate. All of the mice treated between 4 and 24 hours before exposure survived.

The effect slowly declines over five days, Scott says. Giving the stimulant after infection also provides some protection.

The team got similar results testing ALIIS as a protectant against lethal doses of several other types of pneumonia, as well as influenza virus, the mold aspergillus, and the Class A bioterror agents anthrax, bubonic plague, and tularemia.

ALIIS consists of a purified extract of a common bacterium, Haemophilus influenzae, that causes ear and sinus infections in children. The bacterium is essentially broken open, purified and administered as an aerosol.

Preclinical research continues, with early clinical trials - most likely to test a protective role in cancer patients - at least a year away.

The innate immune system indiscriminately targets invading pathogens and also recruits the adaptive immune system to launch a more targeted, pathogen-specific response. The adaptive immune system takes a few days to respond, Dickey says.

"Here the innate immune system is so effective, infections are cleared before the adaptive response even gears up," Dickey says.

The battle also is over before white blood cells called neutrophils, part of the innate immune system, can be called in to help. That's potentially important, Dickey says, because chemotherapy, particularly for leukemia, often wipes out a patient's neutrophils.

Dickey and Scott believe the entire defense against invaders is accomplished by local cells in the lung's lining, called the epithelium. Their research shows the epithelium floods its lining fluid with anti-microbial polypeptides in response to ALIIS inhalation. These natural antibiotics are virtually lying in wait for microbes to kill.

The team is now trying to understand exactly which of these polypeptides kills the pathogens.

Lungs are exposed to infectious agents with every breath, Scott notes, and the innate immune system plays an important role in routinely keeping the lungs healthy.

"We study airway inflammation, and mostly we think about that in a negative context - how to stop inflammation, as in the allergic inflammation that causes asthma," says Dickey. "But surely the ability of airways to become inflamed is there for a good reason. So we asked can we set off a type of inflammation that strengthens protection against infection. The answer is yes."

Source: University of Texas M. D. Anderson Cancer Center

Explore further: Human stem cell model reveals molecular cues critical to neurovascular unit formation

Related Stories

NSA winds down once-secret phone-records collection program

4 hours ago

The National Security Agency has begun winding down its collection and storage of American phone records after the Senate failed to agree on a path forward to change or extend the once-secret program ahead of its expiration ...

Pipeline that leaked wasn't equipped with auto shut-off

4 hours ago

The pipeline that leaked thousands of gallons of oil on the California coast was the only pipe of its kind in the county not required to have an automatic shut-off valve because of a court fight nearly three ...

Uber drivers fined in Hungary

5 hours ago

The Hungarian tax authority fined Uber drivers in its first probe against the ride-sharing service which the economy ministry said Saturday "ignores passenger safety" and must be made to follow regulations.

Recommended for you

Scientists turn blood into neural cells

May 21, 2015

Scientists at McMaster University have discovered how to make adult sensory neurons from human patients simply by having them roll up their sleeve and providing a blood sample.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Drogo
not rated yet Dec 04, 2007
This looks good. Could this be extended to all vaccinations, which at present bypass parts of the natural immune cascade response, by being delivered directly into the bloodstream?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.