Protective Effect of Granulocyte Colony-Stimulating Factor Against T-Cell-Meditated Lethal Shock Triggered by Superantigens

Yoshiyasu Aoki, Kenji Hiromatsu, Noritada Kobayashi, Tomomitsu Hotta, Hidehiko Saito, Hideo Igarashi, Yoshiyuki Niho, Yasunobu Yoshikai

Research output: Contribution to journalArticlepeer-review

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 anti-inflammatory agent against T-cell-mediated toxicity triggered by SAg.

Original languageEnglish
Pages (from-to)1420-1427
Number of pages8
JournalBlood
Volume86
Issue number4
Publication statusPublished - Aug 15 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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