CONTACT: BECKY SOGLIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
Release: Sept. 2, 1999
UI study suggests genetics, gender affect human response
IOWA CITY, Iowa -- Endotoxin -- a common contaminant
of agricultural dust, air pollution and household dust -- causes or exacerbates
asthma and other lung problems in some, but not all, people with respiratory
conditions. A recent University of Iowa Health Care study provides evidence
that when it comes to healthy individuals, pulmonary responses to endotoxin
can also differ markedly, yet consistently.
The study is the first to examine endotoxin response
in nonsmoking, nonasthmatic and nonallergic individuals whose jobs do not
put them in contact with the contaminant. The researchers found that some
people had significant bronchospasm (narrowing of the airway) following slight
endotoxin exposure, while others were resistant to even high dosages. Women
were much more likely than men to show declined airway function after breathing
even small amounts of the contaminant.
"The wide response difference in people who have no
apparent predisposition to lung disease suggests a genetic cause of endotoxin
susceptibility and resistance," said Joel N. Kline, M.D., UI assistant professor
of internal medicine and lead investigator. "The gender-based response difference
also suggests there are cellular differences. The finding may have implications
for the prevention or treatment of endotoxin-associated disease in susceptible
Previous research, including studies led by David
A. Schwartz, M.D., UI professor of internal medicine and a senior author for
the current study, showed that the inhalation of dust containing endotoxin
can cause problems for individuals with asthma or other lung conditions. A
poisonous byproduct of bacterial infection or other microorganisms, endotoxin
is known chemically as lipopolysaccharide. It is extremely prevalent in agricultural
dust, such as that found in grain silos.
In the recent study, 72 individuals, 26 men and 46
women, inhaled incrementally increasing amounts of endotoxin. After each dose,
the researchers measured the participants' pulmonary function. Kline described
the highest endotoxin dosage, 40 micrograms, as "the total amount a worker
inhales during an eight-hour shift in a heavy dust-exposure site such as a
Eight of the participants were highly sensitive and
developed "profound bronchospasm" following exposure to miniscule doses --
6.5 micrograms -- of endotoxin. The majority of participants (53) were intermediate
in their response, while 11 were hyporesponsive, meaning they showed little
response even at the highest dosage. Seven of the eight highly sensitive individuals
were women, while eight of the 11 hyporesponsive individuals were men, pointing
to a sex-based link.
The researchers were able to reproduce the results
with a sub-group of the original participant pool. In addition, to further
document the response differences, the researchers studied blood cell samples
taken from some of the sensitive and nonresponsive individuals. The cells
from sensitive individuals had more inflammatory mediators than cells taken
from the nonresponsive individuals. This cellular finding supported the physiology
results of the breathing tests, Kline said.
He added that it is not entirely clear how endotoxin
causes breathing problems, but the contaminant seems to cause inflammation
through a "cascade" effect.
"The endotoxin causes macrophages, the most numerous
inflammatory cells in the normal lung, to release mediators of inflammation
such as cytokines," Kline explained. "These proteins have multiple effects
including attracting other inflammatory cells."
Overall, the research adds to the "growing acceptance"
that endotoxin is an important component of environmental influences on asthma
and other airway obstructions, he said.
The findings were published in the July issue of the
American Journal of Respiratory and Critical Care Medicine. The research team
included members of the UI College of Medicine departments of internal medicine
and pediatrics and the former department of preventive medicine (now the UI
College of Public Health) and the Veterans Affairs Medical Center in Iowa
City. The study was supported by grants from the federal Department of Veterans
Affairs, the National Institute of Environmental Health Sciences and the National
Heart, Lung and Blood Institute.