Inhibitory effect of antimicrobial agents and anisodamine on the staphylococcal superantigenic toxin-induced overproduction of proinflammatory cytokines by human peripheral blood mononuclear cells.
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.
Kushiya
Koji
K
Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Japan.
Nakagawa
Saori
S
Taneike
Ikue
I
Iwakura
Nobuhiro
N
Imanishi
Ken'ichi
K
Uchiyama
Takehiko
T
Tsukada
Hiroki
H
Gejyo
Fumitake
F
Yamamoto
Tatsuo
T
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
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D012991:Solanaceous Alkaloids; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C003922:anisodamine