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Clinical and Diagnostic Laboratory Immunology, March 2005, p. 399-408, Vol. 12, No. 3
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.3.399-408.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Specific Inhibitory Action of Anisodamine against a Staphylococcal Superantigenic Toxin, Toxic Shock Syndrome Toxin 1 (TSST-1), Leading to Down-Regulation of Cytokine Production and Blocking of TSST-1 Toxicity in Mice

Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata,¹ Department of Microbiology and Immunology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan²

Received 17 October 2004/ Returned for modification 9 November 2004/ Accepted 28 December 2004

Toxic shock syndrome toxin 1 (TSST-1), produced by Staphylococcus aureus (including methicillin-resistant S. aureus), is a superantigenic toxin responsible for toxic shock syndrome as well as neonatal TSS-like exanthematous disease. TSST-1 exhibits its deleterious effects by leading to the abnormal proliferation of, e.g., Vß2⁺ T cells and overproduction of proinflammatory cytokines. In the present study we examined the inhibitory effect of a Chinese herbal extract, anisodamine, on TSST-1 using human peripheral blood mononuclear cells (PBMCs). Anisodamine inhibited the production of proinflammatory cytokines better than interleukin-10 (an anti-inflammatory cytokine). The inhibitory effect of anisodamine was greater than that of any tropane alkaloid examined. Anisodamine acted directly on both monocytes and T cells in human PBMCs, and the effect was confirmed at the transcriptional level. Inhibition of NF-B activation was also demonstrated. In contrast, no significant inhibition of Vß2⁺ T-cell proliferation was observed. In mice injected with TSST-1, anisodamine treatment significantly decreased serum proinflammatory cytokine levels and prevented TSST-1-induced death. These results suggest that anisodamine specifically acts against the production of cytokines (inflammatory cytokines in particular) and not against Vß2⁺ T-cell proliferation and that anisodamine may have a beneficial effect on TSST-1-associated disease.