Compartmentalized lung cytokine release in response to
intravascular and alveolar endotoxin challenge.
Ghofrani, Hossein Ardeschir, Simone Rosseau, Dieter Walmrath, Werner
Kaddus, Antje Kramer, Friedrich Grimminger, J[umlaut]urgen Lohmeyer,
and Werner Seeger.
Department of Internal Medicine, Justus-Liebig University, 35392
Giessen, Germany
APStracts 2:0142L, 1995.
Lung cytokine generation has been implicated in pulmonary injury and
systemic inflammatory responses. In buffer-perfused rabbit lungs,
intravascular endotoxin (10 ng/ml perfusate; total amount 7 [mu]g)
provoked the liberation of 212,100 119,700 pg tumor necrosis factor
-alpha (TNF-) into the vascular space within 3 h. This was augmented
to 3,564,400 1,285,900 pg in the presence of 1% serum.
Bronchoalveolar lavages demonstrated the absence of buffer-admixed
endotoxin and transition of only minor fractions of the vascular TNF-
load into the alveolar space. Aerosolization of 22 [mu]g endotoxin
liberated 824,400 48,750 pg TNF- into the alveolar compartment, which
was even increased to 16,980,000 6,066,350 pg upon co-nebulization of
serum. No endotoxin and only minor amounts of the alveolar TNF-
burden spilled over into the vascular compartment. Vascular pressures
and lung vascular permeability did not change. We conclude that both
intravascular and alveolar endotoxin challenge provokes excessive
lung TNF- generation, manifold amplified in the presence of small
serum quantities. For both routes of application the cytokine
responses were, however, found to be largely compartmentalized under
the given conditions of integer lung barrier properties.
Received 22 May 1995; accepted in final form 8 August 1995.
APS Manuscript Number L160-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.