Treatment with Anti-Interleukin 23 Antibody Ameliorates Disease in Lupus-Prone Mice

Vasileios C Kyttaris,Ourania Kampagianni,George C Tsokos

doi:10.1155/2013/861028

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.

Highlights

Interleukin 23 (IL-23) is a member of the IL-12 family that is important for the generation and maintenance of Th17 cells
Several lines of evidence suggest that Th17 cells may play an important role in Systemic lupus erythematosus (SLE) and in particular lupus nephritis; for example, SLE T cells produce IL-17 spontaneously while IL-17+ T cells are found in the kidneys of SLE patients with nephritis
We have previously shown that lupus-prone mice (B6/lpr) that are genetically deficient in the receptor for IL-23 were protected from the massive lymphoproliferation, production of pathogenic anti-dsDNA antibodies, and the development of nephritis [5]

Summary

Introduction

Interleukin 23 (IL-23) is a member of the IL-12 family that is important for the generation and maintenance of Th17 cells. We have previously shown that lupus-prone mice (B6/lpr) that are genetically deficient in the receptor for IL-23 were protected from the massive lymphoproliferation, production of pathogenic anti-dsDNA antibodies, and the development of nephritis [5]. We provide evidence that treatment of lupus-prone mice with antiIL-23 antibodies ameliorates nephritis through inhibition of the production of IL-17 by T cells.

Results

Conclusion