Acute Hypoxemia in Humans Enhances the Neutrophil Inflammatory Response.
Tamura, Douglas Y. *; Moore, Ernest E. *; Partrick, David A. *; Johnson, Jeffrey L. *; Offner, Patrick J. *; Silliman, Christopher C. +
17(4):269-273, April 2002.
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The neutrophil (PMN) is regarded as a key component in the hyperinflammatory response known as the systemic inflammatory response syndrome. Acute respiratory distress syndrome (ARDS) and subsequent multiple organ failure (MOF) are related to the severity of this hyperinflammation. ICU patients who are at highest risk of developing MOF may have acute hypoxic events that complicate their hospital course. This study was undertaken to evaluate the effects of acute hypoxia and subsequent hypoxemia on circulating PMNs in human volunteers. Healthy subjects were exposed to a changing 02/N2 mixture until their 02 saturation (Sa02) reached a level of 68% saturation. These subjects were then exposed to room air and then returned to their baseline Sa02. PMNs were isolated from pre- and post-hypoxemic arterial blood samples and were then either stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or PMA alone, or they were primed with L-[alpha]-phosphatidylcholine, [beta]-acetyl-[gamma]-O-alkyl (PAF) followed by fMLP activation. Reactive oxygen species generation as measured by superoxide anion production was enhanced in primed PMNs after hypoxemia. Protease degranulation as measured by elastase release was enhanced in both quiescent PMNs and primed PMNs after fMLP activation following the hypoxemic event. Adhesion molecule upregulation as measured by CD11b/CD18, however, was not significantly changed after hypoxemia. Apoptosis of quiescent PMNs was delayed after the hypoxemic event. TNF[alpha], IL-1, IL-6, and IL-8 cytokine levels were unchanged following hypoxemia. These results indicate that relevant acute hypoxemic events observed in the clinical setting enhance several PMN cytotoxic functions and suggest that a transient hypoxemic insult may promote hyperinflammation.
(C) 2002 Lippincott Williams & Wilkins, Inc.