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.
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., Vbeta2+ 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-kappaB activation was also demonstrated. In contrast, no significant inhibition of Vbeta2+ 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 Vbeta2+ T-cell proliferation and that anisodamine may have a beneficial effect on TSST-1-associated disease.
Nakagawa
Saori
S
Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, 757 Ichibanchou, Asahimachidori, Niigata 951-8510, Japan.
Kushiya
Koji
K
Taneike
Ikue
I
Imanishi
Ken'ichi
K
Uchiyama
Takehiko
T
Yamamoto
Tatsuo
T
D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004768:Enterotoxins / Q000037:antagonists & inhibitors*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D018089:Superantigens; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects
D001427:Bacterial Toxins; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D004768:Enterotoxins; D012991:Solanaceous Alkaloids; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C003922:anisodamine