title: Hypoxemia in the absence of blood loss or significant hypotension causes inflammatory cytokine release.
abstract: Although hemorrhagic shock causes a significant elevation of circulating levels of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6], it remains unknown whether hypoxemia per se in the absence of blood loss activates macrophages (Mø) to release increased amounts of these mediators. To study this, hypoxemia was induced in C3H/HeN mice by placing them in a plastic box that was flushed with a gas mixture containing 95% N2-5% O2 for 60 min, 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 h thereafter, blood samples were obtained, plasma was separated, and then peritoneal Mø (pMø) and Kupffer cells (KC) were isolated and incubated at 37 degrees C for 24 h with lipopolysaccharide. The Mø supernatants, as well as plasma samples, were assayed for TNF-alpha, IL-1 beta, and IL-6 with the use of 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 h after hypoxemia compared with shams. Moreover, the release of TNF-alpha, IL-1 beta, and IL-6 by pMø and KC was markedly increased after hypoxemia compared with 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.
authors.affiliation: Department of Surgery, Michigan State University, East Lansing 48824, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ertel
authors.forename: M H
authors.initials: MH
authors.lastname: Morrison
authors.forename: A
authors.initials: A
authors.lastname: Ayala
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D001794:Blood Pressure; D016207:Cytokines / Q000378:metabolism*; D005740:Gases / Q000097:blood; D006470:Hemorrhage / Q000150:complications; D007022:Hypotension / Q000150:complications; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D005740:Gases; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha