Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice

• Published in: The Journal of experimental medicine Vol. 179; no. 1; pp. 305 - 310
• Main Authors: Ishida, H, Muchamuel, T, Sakaguchi, S, Andrade, S, Menon, S, Howard, M
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01-01-1994
• Subjects: Animals; Antibodies - administration & dosage; Autoimmunity - drug effects; Autoimmunity - immunology; Female; Interleukin-10 - immunology; Mice; Mice, Inbred BALB C; Neutralization Tests; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.179.1.305

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.