Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice.
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- H Ishida
- DNAX Research Institute, Palo Alto, California 94304.
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- T Muchamuel
- DNAX Research Institute, Palo Alto, California 94304.
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- S Sakaguchi
- DNAX Research Institute, Palo Alto, California 94304.
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- S Andrade
- DNAX Research Institute, Palo Alto, California 94304.
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- S Menon
- DNAX Research Institute, Palo Alto, California 94304.
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- M Howard
- DNAX Research Institute, Palo Alto, California 94304.
抄録
<jats:p>We have previously shown that continuous administration of anti-interleukin 10 (anti-IL-10) antibodies (Abs) to BALB/c mice modifies endogenous levels of autoantibodies, tumor necrosis factor alpha (TNF-alpha), and interferon gamma, three immune mediators known to affect the development of autoimmunity in "lupus-prone" New Zealand black/white (NZB/W)F1 mice. To explore the consequences of IL-10 neutralization in NZB/W F1 mice, animals were injected two to three times per week from birth until 8-10 mo of age with anti-IL-10 Abs or with isotype control Abs. Anti-IL-10 treatment substantially delayed onset of autoimmunity in NZB/W F1 mice as monitored either by overall survival, or by development of proteinuria, glomerulonephritis, or autoantibodies. Survival at 9 mo was increased from 10 to 80% in anti-IL-10-treated mice relative to Ig isotype-treated controls. This protection against autoimmunity appeared to be due to an anti-IL-10-induced upregulation of endogenous TNF-alpha, since anti-IL-10-protected NZB/W F1 mice rapidly developed autoimmunity when neutralizing anti-TNF-alpha Abs were introduced at 30 wk along with the anti-IL-10 treatment. Consistent with the protective role of anti-IL-10 treatment in these experiments, continuous administration of IL-10 from 4 until 38 wk of age accelerated the onset of autoimmunity in NZB/W F1 mice. The same period of continuous IL-10 administration did not appear to be toxic to, or cause development of lupus-like autoimmunity in normal BALB/c mice. These data suggest that IL-10 antagonists may be beneficial in the treatment of human systemic lupus erythematosus.</jats:p>
収録刊行物
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- The Journal of experimental medicine
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The Journal of experimental medicine 179 (1), 305-310, 1994-01-01
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1360574096161653888
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- NII論文ID
- 30017432003
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- ISSN
- 15409538
- 00221007
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