A platelet activating factor receptor antagonist inhibits cytokine production in human whole blood by bacterial toxins and live bacteria.
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 microL) 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 degrees 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.


CONCLUSIONS
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.
Ogata
Masanori
M
From the Department of Anesthesiology, University of Occupational and Environmental Health, Japan.
Nandate
Koichiroh
K
Kawasaki
Takashi
T
Kawasaki
Chika
C
Ozaki
Masayuki
M
Shigematsu
Akio
A
D000942:Antigens, Bacterial / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood*; D004768:Enterotoxins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011726:Pyridinium Compounds / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D043562:Receptors, G-Protein-Coupled; D044005:Tetrahydroisoquinolines; C039351:platelet activating factor receptor; C031818:enterotoxin B, staphylococcal; C067430:TCV 309