Germ-Fighting Inhaler Could Fend Off Bioterror Agents

Germ-Fighting Inhaler Could Fend Off Bioterror Agents
MONDAY, Dec. 3 (HealthDay News) -- Mention inhalers and mostpeople think of asthma, but new research shows that inhalers could becomeinfection-fighting, lifesaving gear for firemen, emergency workers andother first responders.
They could also help protect people whose immune systems are weakenedby chemotherapy or HIV, according to scientists who've tested the newinhaler in mice.
"We showed we can protect mice against all four major classes ofpathogens: Gram positive bacteria, Gram negative bacteria, fungus andvirus. So, it has protected against everything we tried," said studyauthor Brenton Scott, a post-doctoral fellow in the pulmonary medicinedepartment of the University of Texas M.D. Anderson Cancer Center.
His team was slated to present its findings Monday at the AmericanSociety for Cell Biology's annual meeting in Washington, D.C.
Pneumonia, especially, is a significant cause of death for chemotherapypatients, so the researchers decided to see if they could protect patientsagainst the disease by boosting immune activity in the lungsbeforehand.
The team exposed mice to an aerosolized formulation called AerosolizedLung Innate Immune Stimulant (ALIIS), a soluble bacterial extract.
They then challenged the mice with inhaled Streptococcuspneumoniae, the pathogen that causes pneumonia.
The untreated mice all died of the infection, but 83 percent of themice that were exposed two hours following treatment survived, as did 100percent of mice exposed between four and 24 hours later. Protection lastedas long as five days, the team said, and was also effective against abroad range of pathogens, including the bacteria responsible for anthrax,plague, tularemia, the fungus Aspergillus and influenza virus.
According to Scott, this broad-spectrum protection means ALIIS couldpotentially be used by first responders in the event of a bioterrorattack.
"First responders could potentially take a dose of ALIIS and beprotected without knowing what the bugs are, and buy a window ofopportunity to see what bacteria are out there," said Scott, who envisionsa delivery system akin to an asthma inhaler.
But Steven Mizel, a professor of microbiology and immunology at WakeForest University Health Sciences in Winston-Salem, NC, was skeptical.
"If first responders get a cut on their finger, they are still dead,"he said.
That's because the protection afforded by ALIIS is limited to inhaledpathogens; challenge with injected bacteria still resulted in death, Scottnoted. But Scott believes this finding is also a benefit, as it suggeststhe drug induces only a localized immune response, rather than apotentially damaging, whole-body one.
Scott also noted that ALIIS neither induced mucus formation notexacerbated asthma, and that repeated exposure of mice to the treatmentappeared to cause little long-term damage beyond fibrosis, a thickening ofthe airways.
ALIIS induces massive stimulation of the so-called innate immuneresponse, a hodge-podge of antimicrobial peptides (proteins), growthfactors, and white blood cells that collectively, though non-specifically,deal with potential pathogens. Indeed, it does this so well, Scott said,that microbes died virtually on contact with the lining of the airway.
But ALIIS has no effect on the other arm of immunity, the adaptiveresponse of B and T lymphocytes that are responsible for protectiveantibodies and long-term immunological memory. As a result, Mizel said,its potential real-world efficacy could be limited.
"I think this research supports the contention that the innate immuneresponse is being triggered, and that is a good holding action," Mizelsaid. But he added that, "you need adaptive immunity to kick ineventually," especially if the body is exposed to large doses of pathogen,as is likely during a bioterror incident.
"If you are at the epicenter of the attack, and there are highconcentrations of bacteria around, I would be shocked if the innate immunesystem could handle that," he said.
Study senior author Dr. Burton Dickey and Scott have formed a companycalled Pulmotect to commercialize ALIIS. Clinical trials are in theplanning stages, Scott said, but will have to wait at least until safetyand efficacy studies in other animal models can be completed.