Cytokine response by human monocytes to Clostridium difficile toxin A and toxin B.
Clostridium difficile toxins A and B isolated from strain VPI 10463 were tested for induction of cytokine release by human monocytes. Toxin B at 10(-12) M activated human monocytes as measured by release of interleukin-1 (IL-1), tumor necrosis factor (TNF), or IL-6. These effects of toxin B were heat labile (51 degrees C, 30 min). Toxin B was as effective as bacterial lipopolysaccharides in inducing IL-1 beta but less effective in inducing TNF or IL-6. Toxin B and lipopolysaccharides were synergistic in induction of IL-1 beta, TNF, and IL-6. The toxin A preparation used was 1,000-fold less active than toxin B. Apart from the difference in activity, the two toxins showed identical patterns of reaction and there was no synergism between them. A short pulse with toxin B was sufficient to trigger IL-1 release. Toxin B was also extremely toxic for monocytes. The toxicity and the induced proinflammatory monokines (IL-1 and TNF) may contribute to the pathogenic mechanisms of C. difficile infection and pseudomembranous colitis.
Flegel
W A
WA
Abteilung für Transfusionsmedizin, Universität Ulm, Germany.
Müller
F
F
Däubener
W
W
Fischer
H G
HG
Hadding
U
U
Northoff
H
H
D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000633:toxicity*; D001790:Blood Physiological Phenomena; D016360:Clostridioides difficile / Q000472:pathogenicity*; D003603:Cytotoxins / Q000633:toxicity*; D004357:Drug Synergism; D004768:Enterotoxins; D006358:Hot Temperature; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D004768:Enterotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile