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.