Treatment with anti-interleukin 23 antibody ameliorates disease in lupus-prone mice - PubMed (original) (raw)

Treatment with anti-interleukin 23 antibody ameliorates disease in lupus-prone mice

Vasileios C Kyttaris et al. Biomed Res Int. 2013.

Abstract

Interleukin 23 receptor expressing IL-17 producing T cells have been shown to be important in the development of murine lupus. The usefulness of IL-23 inhibition in ameliorating lupus nephritis is unknown. We hypothesized that inhibition of IL-23 will ameliorate nephritis in lupus-prone mice. To this end, we treated MRL/lpr lupus-prone mice for 6 weeks with a rat anti-IL-23p19 antibody, which resulted in delaying the onset of nephritis without affecting the production of anti-dsDNA antibodies. The effect of the treatment was hampered by the production of murine anti-rat IgG antibodies. The amelioration of murine lupus by IL-23 inhibition strengthens the rationale for targeting IL-23 in patients with systemic lupus erythematosus.

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Figures

Figure 1

Figure 1

A monoclonal anti-IL-23p19 antibody limits the IL-23-induced production of IL-17 by MRL/lpr splenocytes. One million MRL/lpr splenocytes were activated in vitro in the presence of plate bound anti-CD3 and anti-CD28 antibodies (see Section 2). IL-23 was added in the medium as indicated at a concentration of 10 ng/mL. At 24 hours later, the concentration of IL-17 was measured in the supernatants using ELISA. Asterisk (∗) signifies statistical significance.

Figure 2

Figure 2

Six MRL/lpr mice were treated for the indicated time with 20 _μ_g of anti-IL-23p19 antibody given intraperitoneally three times weekly or control rat IgG. Urine was collected weekly. (a) The presence of leucocytes was assessed using a semiquantitative method. (b) Albumin and creatinine were measured using a colorimetric technique and the ratio is presented here. (c) dsDNA antibody levels were measured in the serum using a sandwich ELISA.

Figure 3

Figure 3

(a) At the end of the treatment, the MRL/lpr mice were sacrificed and the splenocytes were stimulated in vitro with anti-CD3/CD28 antibodies for 24 hours. IL-17A was measured in the supernatant by ELISA. (b) Serum levels of anti-rat IgG were measured by sandwich ELISA as described in Section 2.

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