Sacco, S and Heremans, H and Echtenacher, B and Buurman, WA and Amraoui, Z and Goldman, M and Ghezzi, P (1997) Protective effect of a single interleukin-12 (IL-12) predose against the toxicity of subsequent chronic IL-12 in mice: Role of cytokines and glucocorticoids. BLOOD, 90 (11). pp. 4473-4479. ISSN 0006-4971,
Full text not available from this repository.Abstract
The mechanisms of interleukin-12 (IL-12) toxicity were studied in mice using a schedule (murine rlL-12, 400 ng/mouse, intraperitoneally [IP] once daily for 5 days) that markedly reduced body weight and food intake. On day 5, IL-12-treated mice had elevated serum and spleen IFN-gamma and tumor necrosis factor (TNF). Serum sTNFR-P75 and corticosterone (CS) were also elevated. IL-12 toxicity was partially prevented by anti-IFN-gamma antibodies or dexamethasone (DEX). A pre-dose of IL-12 (200 ng/mouse on day -14) completely prevented the toxicity of subsequent IL-12. The IL-12 predose also inhibited IL-12-induced IFN-gamma levels, but did not modify IL-12-induced CS, TNF or sTNFR-P75. A protective effect was observed with a predose of lipopolysaccharide (LPS) or murine recombinant (r)IL-10. The protective effect of the IL-12 predose was reduced by coadministration of anti-IFN-gamma, but a predose of murine rIFN-gamma was not protective, suggesting that IFN-gamma is necessary but not sufficient for the protective effect of IL-12. The IL-12 predose specifically protected against IL-12 toxicity and did not modify LPS toxicity. These data indicate that IL-12 can induce tolerance to its own toxicity, probably through a downregulation of IL-12-induced IFN-gamma but independently of endogenous glucocorticoids. IFN-gamma, and possibly IL-10, might be important in this tolerance. (C) 1997 by The American Society of Hematology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA PRODUCTION; CELL STIMULATORY FACTOR; EXPERIMENTAL VIRAL-INFECTIONS; PITUITARY-ADRENAL AXIS; IFN-GAMMA; FACTOR-ALPHA; EXPERIMENTAL ENDOTOXEMIA; IN-VIVO; LIPOPOLYSACCHARIDE; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/50345 |
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