CONTACT: BECKY SOGLIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
Release: Sept. 8, 1999
UI study advances understanding of antimicrobials and
cystic fibrosis-related infection
IOWA CITY, Iowa -- Human airway secretions include
antimicrobial agents that normally protect the lungs from infection caused
by inhaled bacteria and other microorganisms. A recent University of Iowa
Health Care study suggests that high salt concentrations in the airways of
people with cystic fibrosis prevent these antimicrobial factors from working
"The finding provides some new ideas about treatments
for cystic fibrosis," said
Sue M. Travis, Ph.D., UI research scientist and principal investigator.
Cystic fibrosis is the most common fatal inherited
disease among Caucasians of Northern European descent and occurs in about
one of every 2,000 births. Advances in treating the disease complications
have increased the average survival age well beyond childhood; however, there
is no cure.
In people with cystic fibrosis, whose lungs often
become infected by inhaled microorganisms, airway antimicrobial activity has
not been well understood. Previous research, including UI studies, showed
that cystic fibrosis disrupts defenses against infection because the thin
layer of liquid that lines the airways is saltier than in non-cystic fibrosis
airways. Under normal conditions, antimicrobial peptides and proteins destroy
the invasive microorganisms that land on the airway surface.
"Saltiness impairs the ability of the airway surface
liquid to kill bacteria," Travis said. "We investigated specifically whether
antimicrobials could kill bacteria in the salty conditions caused by cystic
The investigators studied how previously identified
antimicrobial proteins, including lysozyme and lactoferrin, functioned in
test-tube samples of human airway secretions taken from healthy people and
people with cystic fibrosis.
"We found that the airway secretions, and the individual
antimicrobial proteins, could kill bacteria in low-salt conditions, but they
were less able to kill bacteria in high-salt concentrations," Travis said.
"This inhibition of the antimicrobials by high salt may be why they fail to
prevent infections in cystic fibrosis airways."
Travis explained how the findings could lead to potential
"Lowering the salt concentration in the cystic fibrosis
airway might allow the antimicrobial factors to kill bacteria," she said.
"Second, treatment using antimocribal factors that can function well in high-salt
liquid could be beneficial."
"This work helps lay the foundation on which new treatments
can be built for cystic fibrosis," said co-investigator Michael J. Welsh,
M.D., UI professor of internal medicine, and physiology and biophysics.
Welsh, who is also a Howard Hughes Medical Institute
investigator, led a previous study that suggests that the absence or malfunction
of a specialized chloride channel in the cystic fibrosis airway causes the
increased saltiness and that treatment could be based on correcting this salt
In addition to Travis and Welsh, the other UI investigators
for the antimicrobial study included Barbara-Ann D. Conway, Ph.D., postdoctoral
associate in microbiology; Joseph Zabner, M.D., assistant professor of internal
medicine; Jeffrey J. Smith, M.D., associate professor (clinical) of pediatrics;
Norma N. Anderson, researcher in internal medicine; Pradeep K. Singh, M.D.,
fellow in internal medicine, and E. Peter Greenberg, Ph.D., professor of microbiology.
The study was funded in part by a grant from the Cystic
Fibrosis Foundation. The findings were published in the May issue of the American
Journal of Respiratory, Cell and Molecular Biology. The May issue also included
a perspective on the study by Charles L. Bevins, M.D., Ph.D., of the Lerner
Research Institute at the Cleveland Clinic Foundation.