Protective effect of granulocyte colony-stimulating factor against T- cell-meditated lethal shock triggered by superantigens

Y. Aoki, K. Hiromatsu, N. Kobayashi, T. Hotta, H. Saito, H. Igarashi, Y. Niho, Y. Yoshikai

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    30 Citations (Scopus)

    Abstract

    The bacterial superantigens (SAg), toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin B (SEB), are powerful T-cell stimulators, triggering systemic release of lymphokines causing lethal shock in D- galactosamine (D-Gal)-sensitized mice. We show that pretreatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) protects mice against T-cell-mediated SAg-shock. In mice challenged with D-Gal/TSST- 1, lethal shock was caused within 30 hours. In contrast, animals pretreated with two consecutive subcutaneous injections of 2 μg rhG-CSF with a 12-hour time interval showed only marginal signs of illness and no lethality after challenge with D-Gal/TSST-1. Mice treated with 5 μg rhG-CSF either 12 or 6 hours in advance also survived otherwise lethal doses of D-Gal/TSST-1. The protective effects of rhG-CSF pretreatment was also evident against lethal doses of D-Gal/SEB challenge and this protection was accompanied by suppression of systemic interleukin-2. However, rhG-CSF affected neither the proliferative responses of SAg-reactive T cells in vivo or in vitro nor their interleukin-2 production in vitro, implying that rhG-CSF may indirectly interfere with cytokine synthesis in T cells but not with T-cell-SAg binding itself. These results represent another beneficial effect of rhG-CSF as an antiinflammatory agent against T-cell-mediated toxicity triggered by SAg.

    Original languageEnglish
    Pages (from-to)1420-1427
    Number of pages8
    JournalBlood
    Volume86
    Issue number4
    DOIs
    Publication statusPublished - 1995

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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