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Anesth Analg 2004;98:1767-1772
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000112310.93297.AF

ECONOMICS, EDUCATION, AND HEALTH SYSTEMS RESEARCH

A Platelet Activating Factor Receptor Antagonist Inhibits Cytokine Production in Human Whole Blood by Bacterial Toxins and Live Bacteria

Masanori Ogata, MD, Koichiroh Nandate, MD, Takashi Kawasaki, MD, Chika Kawasaki, MD, Masayuki Ozaki, MD, and Akio Shigematsu, MD

From the Department of Anesthesiology, University of Occupational and Environmental Health, Japan

Address correspondence and reprint requests to Masanori Ogata, MD, Department of Anesthesiology, University of Occupational and Environmental Health, 1–1 Iseigaoka, Yahatanishiku, Kitakyushu 807–8555, Japan. Address email to mogata{at}med.uoeh-u.ac.jp

We previously reported that a platelet-activating factor receptor (PAFR) antagonist (TCV-309) suppressed lipopolysaccharide (LPS)-induced mortality and tumor necrosis factor (TNF) production in mice. However, the effect of TCV-309 on cytokine production induced by Staphylococcus enterotoxin B (SEB) or live bacteria has not been reported. In this study we investigated the effect of TCV-309 on cytokine production in human whole blood induced by LPS, SEB, and both Gram-positive and -negative bacteria. Human whole blood diluted 5:1 (980 µL) was placed in the wells of a 24-well plate. Ten microliters of LPS, SEB, Escherichia coli O18 K+, or Staphylococcus aureus were added to each well. After incubation at 37°C for 6 h, TNF, interleukin (IL)-6, and IL-8 in the culture medium were measured. TCV-309 did not affect the growth of either E. coli or S. aureus bacteria in the culture medium for the 6 h incubation. LPS, SEB, and both E. coli and S. aureus induced TNF, IL-6, and IL-8 in human whole blood. TCV-309 significantly inhibited the production of TNF, IL-6, and IL-8 induced by LPS, SEB, and bacteria. A PAFR antagonist suppressed cytokine production induced by LPS, SEB, and both Gram-positive and -negative bacteria in human whole blood. A PAFR plays an important role of producing proinflammatory cytokines induced by both toxins and live bacteria.

IMPLICATIONS: The platelet-activating factor receptor plays an important role in producing proinflammatory cytokines induced by bacterial toxins, such as lipopolysaccharide,Staphylococcus enterotoxin B, and live Gram-positive and Gram-negative bacteria.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2004 by the International Anesthesia Research Society.