Effects of interleukin 5-induced pulmonary eosinophilia on airway
reactivity in the guinea pig.
Lilly, Craig M., Richard W. Chapman, Susan J. Sehring, Peter J.
Mauser, Robert W. Egan, and Jeffrey M. Drazen.
Combined Program in Pulmonary and Critical Care Medicine,
Department of Medicine, Brigham and Women's Hospital, and Harvard
Medical School, Boston, Massachusetts 02115, Schering-Plough Research
Institute, Kenilworth, New Jersey 07033
APStracts 2:0180L, 1995.
Administration of interleukin 5 (IL-5) to guinea pigs by tracheal
injection was associated with increased recovery of eosinophils and
neutrophils from bronchoalveolar lavage (BAL) fluid. The number of
eosinophils recovered from BAL fulid increased in a dose-dependent
manner from 9 +/- 2 X 103 /ml to a plateau of 143 +/- 29 X 103 /ml
after the administration of recombinant human IL-5 (rh IL-5).
Tracheal administration of recombinant guinea pig IL-5 (gp IL-5) also
increased eosinophil recovery but was less potent than rh IL-5.
Histological analysis confirmed the presence of inflammatory cells in
the lung; there were higher grades of inflammation in airway than in
parenchymal tissue after gp IL-5 administration. In addition, the
histological grade of airway inflammation was greater 24 and 72 hours
after gp IL-5 administration than it was 6 days after administration.
Airway hyperresponsivness is reported to occur in guinea pigs exposed
to rh IL-5 by intraperitoneal cellular production. It is surprising
that airway infiltration with eosinophils induced by the topical
application of IL-5 was not associated with hyperresponsiveness to
substance P, histamine, or platelet-activating factor (PAF) in intact
animals or to methacholine in tracheally perfused lungs. Furthermore,
the microvascular leakage induced by substance P was not altered by
rh IL-5 administration. These findings indicate that the presence of
eosinophils alone is not sufficient for the expression of airway
hyperresponsiveness. Our ability to separate eosinophil recruitment
and retention in the tissues from airway hyperresponsiveness
indicates that these two processes are distinct and that the presence
of eosinophils in lung tissue, by itself, is not sufficient to alter
airway contractile responses.
Received 19 June 1995; accepted in final form 21 September 1995.
APS Manuscript Number L190-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95