Aerosol Launches Immune Response in Lungs to Wipe Out Lethal Infections

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Source: University of Texas M. D. Cancer Center

Released: Thu 29-Nov-2007, 10:55 ET

Embargo expired: Mon 03-Dec-2007, 10:00 ET

Newswise* (press release)

Aerosol Launches Immune Response in Lungs to Wipe Out Letha

Infections

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Medical News Keywords

PNEUMOCOCCAL PNEUMONIA, AMERICAN SOCIETY FOR CELL BIOLOGY, BRENTON

SCOTT, PH.D.

http://www.newswise.com/articles/view/535760/

Description

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. Cancer Center reports at a major

scientific meeting.

Newswise — 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. 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 , Ph.D., post-doctoral fellow in M. D.

'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, 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 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,

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. "

Research is funded by the and Barbara Bush Endowment for

Innovative Cancer Research, M. D. 's Odyssey Fellowship

program, and grants from the National Institutes of Health, National

Heart, Lung and Blood Institute.

Dickey and others involved in the research have a patent on ALIIS.

Dickey, and co-author Tuvim, Ph.D., associate

professor in the Department of Pulmonary Medicine, own stock in

Pulmotect, LLC, which has licensed the ALIIS technology from M. D.

. These arrangements are managed in accordance with M. D.

's conflict of interest policies.

Co-authors with , Dickey and Tuvim are Cecilia Clement, M.D.,

and , M.D., both of M. D. 's Department of

Pulmonary Medicine; E. Gilbert, Ph.D. of Baylor College of

Medicine's Department of Molecular Virology and Microbiology; and

ny , Ph.D., The University of Texas Medical Branch at

Galveston Department of Microbiology and Immunology.