Hypoxemia in the absence of blood loss or significant hypotension
causes inflammatory cytokine release.
Ertel, Wolfgang, Mary H. Morrison, Alfred Ayala, and Irshad H.
Chaudry.
Shock and Trauma Research Institute, Departments of Surgery,
Microbiology, and Physiology, Michigan State University, East
Lansing, Michigan 48824, Present address: Division of Trauma Surgery,
Department of Surgery, Universit[umlaut]atsspital Z[umlaut]urich,
R[umlaut]amistrasse 100, CH-8091 Z[umlaut]urich, Switzerland
APStracts 2:0054R, 1995.
Although hemorrhagic shock causes a significant elevation of
circulating levels of proinflammatory cytokines (TNF-[alpha], IL
-1[beta], IL-6), it remains unknown whether hypoxemia per?se in the
absence of blood loss activates macrophages (M) to release increased
amounts of these mediators. To study this, hypoxemia was induced in
C3H/HeN mice by placing them in a plastic box which was flushed with
a gas mixture containing 95% N2:5% O2 for 60 minutes, followed by
return of the mice to room air. For control animals, the plastic box
was flushed with room air. At 0, 2 or 24?hr thereafter, blood samples
were obtained, plasma separated and then peritoneal M (pM) and
Kupffer cells (KC) were isolated and incubated at 37 degrees C for
24?hr with lipopolysaccharide. The M supernatants, as well as plasma
samples, were assayed for TNF-[alpha], IL-1[beta], and IL-6 using
specific bioassays. Hypoxemia induced a significant (p<0.05) increase
in plasma TNF-[alpha] levels during the entire study period, while
circulating IL-6 was elevated by 313% (p<0.01) at 24 hr after
hypoxemia compared to shams. Moreover, the release of TNF-[alpha],
IL-1[beta], and IL-6 by pM and KC was markedly increased after
hypoxemia compared to shams. Thus, hypoxemia in itself, in the
absence of any blood loss, or tissue injury, induces release of
proinflammatory cytokines which may contribute to systemic
inflammation following hypoxemia.
Received 15 June 1994; accepted in final form 21 February 1995.
APS Manuscript Number R336-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 7 March 1995.