Protective effect of granulocyte colony-stimulating factor against T-cell-meditated lethal shock triggered by superantigens.
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 micrograms 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 micrograms 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.
Aoki
Y
Y
Laboratory of Host Defense, Nagoya University School of Medicine, Japan.
Hiromatsu
K
K
Kobayashi
N
N
Hotta
T
T
Saito
H
H
Igarashi
H
H
Niho
Y
Y
Yoshikai
Y
Y
D000818:Animals; D001427:Bacterial Toxins; D004768:Enterotoxins / Q000037:antagonists & inhibitors; D005260:Female; D005434:Flow Cytometry; D005690:Galactose; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007376:Interleukin-2 / Q000097:blood; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000209:etiology; D012769:Shock / Q000517:prevention & control*; D018089:Superantigens; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001427:Bacterial Toxins; D004768:Enterotoxins; D007376:Interleukin-2; D008222:Lymphokines; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D016179:Granulocyte Colony-Stimulating Factor; C031818:enterotoxin B, staphylococcal; D005690:Galactose