title: Cytokine response by human monocytes to Clostridium difficile toxin A and toxin B.
abstract: 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.
authors.affiliation: Abteilung für Transfusionsmedizin, Universität Ulm, Germany.
authors.forename: W A
authors.initials: WA
authors.lastname: Flegel
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: W
authors.initials: W
authors.lastname: Däubener
authors.forename: H G
authors.initials: HG
authors.lastname: Fischer
authors.forename: U
authors.initials: U
authors.lastname: Hadding
authors.forename: H
authors.initials: H
authors.lastname: Northoff
mesh_terms: 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*
chemical_list: 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