Differential effects of in vivo ethanol on lps-induced tnf and
nitric oxide production in the lung..
Kolls, Jay K., M. D., Jainming Xie, M. D., Dinghua Lei, M. D., Stanley
Greenberg, Ph. D., Warren R. Summer, M. D., Steve Nelson, M. D.
LSU Section of Pulmonary/Critical Care and the LSU Alcohol Research
Center MEB, Room 3205, 1901 Perdido Street, New Orleans, LA 70112,
Phone-504-568-4634, Fax-504-568-4295
APStracts 2:0024L, 1995.
Alcohol (ETOH) has been shown to suppress LPS-induced nitric oxide
generation and tumor necrosis factor (TNF) production in the lung in
vivo. We have previously reported that ETOH suppressed gene
expression for inducible nitric oxide synthase (iNOS) with a
subsequent decrease in release of reactive nitrogen intermediates by
alveolar macrophages and recruited lung neutrophils. We hypothesized
that a similar mechanism may be involved in ETOH-induced suppression
of LPS-stimulated TNF production. In contrast to what we found with
iNOS, ETOH had no effect on TNF mRNA in alveolar macrophages or
recruited lung neutrophils. However, immunoreactive and bioactive TNF
was reduced by 72%. ETOH treatment resulted in an increased level of
the membrane bound 26 kDa form of TNF which suggested that
proteolytic cleavage of this prohormone was affected by ETOH.
Experiments with t-butyl alcohol, a tertiary alcohol that is not
metabolized to acetaldehyde, yielded similar results. Thus, ETOH
appears to be the active substance in suppression of TNF in the lung
in vivo. Pre-treatment with intratracheal interferon-gamma 24 hours
prior to intratracheal LPS increased TNF bioactivity partly due to
increased TNF mRNA and by increasing TNF processing as evidenced by a
decrease in the 26 kDa TNF prohormone and an increase in
immunoreactive and bioactive TNF.
Received 25 October 1994; accepted in final form 2 February 1995.
APS Manuscript Number L308-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.