Amiloride inhibits cytokine production in epithelium infected with
respiratory syncytial virus.
Mastronarde, John G., Marty M. Monick, Thomas J. Gross, and Gary W.
Hunninghake.
Division of Pulmonary, Critical Care and Occupational Medicine,
University of Iowa College of Medicine and Veterans Affairs
Administration Medical Center, Iowa City, Iowa 52242
APStracts 3:0051L, 1996.
Respiratory syncytial virus (RSV) is an important respiratory pathogen
in infants and children. RSV preferentially infects airway epithelium
and causes local production of inflammatory cytokines. Ribavirin, the
only specific agent available for treatment of RSV infection, has
limited effectiveness. There is little data regarding the ability of
drugs to modulate the inflammatory response of epithelium infected
with RSV. This study evaluated the effect of amiloride and ribavirin
on cytokine production by RSV-infected epithelium. We observed a dose
dependent reduction in IL-8 protein release with both amiloride and
ribavirin in RSV-infected A549 epithelial cells. Peak effects were
observed at concentrations of 200 mM amiloride and 60 mM ribavirin.
Both amiloride and ribavirin inhibited IL-8 mRNA induction.
Pretreatment with either agent was not required to inhibit IL-8
release. Both drugs also inhibited IL-6 release. However, unlike
ribavirin, amiloride did not inhibit viral replication or infection.
Amiloride also inhibited IL-8 release from A549 cells stimulated with
IL-1 or TNF. Amiloride similarly inhibited IL-8 protein release from
primary human airway epithelium infected with RSV. These data
demonstrate that both amiloride and ribavirin inhibit cytokine
production in RSV-infected airway epithelium. These results suggest
amiloride, as well as ribavirin, may be useful as a theurapeutic
agent in RSV infections.
Received 27 July 1995; accepted in final form 1 March 1996.
APS Manuscript Number L233-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96