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

TLDR

The study aimed 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 months of age with anti‑IL‑10 antibodies or isotype controls. Continuous anti‑IL‑10 antibody treatment delayed autoimmunity onset in NZB/W F1 mice, increasing 9‑month survival from 10 % to 80 % and reducing proteinuria, glomerulonephritis, and autoantibody levels, an effect linked to TNF‑α up‑regulation, whereas continuous.

Abstract

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.