title: Inhibitory effect of antimicrobial agents and anisodamine on the staphylococcal superantigenic toxin-induced overproduction of proinflammatory cytokines by human peripheral blood mononuclear cells.
abstract: Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), produces superantigenictoxins, such as toxic shock syndrome toxin-1 (TSST-1). TSST-1 abnormally activates T cells to overproduce inflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) leading to shock. In this study, we investigated the inhibitory effect of antimicrobial agents and anisodamine (a Chinese herbal extract) on TSST-1-induced cytokine production. Among the macrolides and related agents examined, azithromycin and rokitamycin showed the greatest inhibitory activity against the TSST-1-induced cytokine production. This inhibitory effect was similar to that of anisodamine, which, however, had no inhibitory activity against bacterial growth. Vancomycin, teicoplanin, arbekacin, and linezolid (anti-MRSA and related agents) had no significant inhibitory effect on cytokine production. The inhibitory effect of the drugs on cell proliferation was not significant. These data indicate that some antimicrobial agents, e.g., azithromycin and rokitamycin, manifest anti-superantigenic toxin activity through the inhibition of cytokine production, just like anisodamine.
authors.affiliation: Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kushiya
authors.forename: Saori
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Ikue
authors.initials: I
authors.lastname: Taneike
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Iwakura
authors.forename: Ken'ichi
authors.initials: K
authors.lastname: Imanishi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tsukada
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004768:Enterotoxins / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D018089:Superantigens
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D012991:Solanaceous Alkaloids; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C003922:anisodamine