Limits...
IL-23 dependent and independent stages of experimental arthritis: no clinical effect of therapeutic IL-23p19 inhibition in collagen-induced arthritis.

Cornelissen F, Asmawidjaja PS, Mus AM, Corneth O, Kikly K, Lubberts E - PLoS ONE (2013)

Bottom Line: Neutralizing IL-23 after onset of CIA in rats has been shown to reduce paw volume, but the effect on synovial inflammation and the immunological autoimmune response is not clear.Importantly, neutralizing IL-23 after the first signs of CIA did not ameliorate the disease.These data suggest that specific neutralization of IL-23p19 after onset of autoimmune arthritis may not be beneficial as a therapeutic therapy for patients with rheumatoid arthritis (RA).

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.

ABSTRACT
IL-23p19 deficient mice have revealed a critical role of IL-23 in the development of experimental autoimmune diseases, such as collagen-induced arthritis (CIA). Neutralizing IL-23 after onset of CIA in rats has been shown to reduce paw volume, but the effect on synovial inflammation and the immunological autoimmune response is not clear. In this study, we examined the role of IL-23 at different stages of CIA and during T cell memory mediated flare-up arthritis with focus on changes in B cell activity and Th1/Th17 modulation. Anti-IL-23p19 antibody (anti-IL23p19) treatment, starting 15 days after the type II collagen (CII)-immunization but before clinical signs of disease onset, significantly suppressed the severity of CIA. This was accompanied with significantly lower CII-specific IgG1 levels and lower IgG2a levels in the anti-IL-23p19 treated mice compared to the control group. Importantly, neutralizing IL-23 after the first signs of CIA did not ameliorate the disease. This was in contrast to arthritic mice that underwent an arthritis flare-up since a significantly lower disease score was observed in the IL-23p19 treated mice compared to the control group, accompanied by lower synovial IL-17A and IL-22 expression in the knee joints of these mice. These data show IL-23-dependent and IL-23-independent stages during autoimmune CIA. Furthermore, the memory T cell mediated flare-up arthritis is IL-23-mediated. These data suggest that specific neutralization of IL-23p19 after onset of autoimmune arthritis may not be beneficial as a therapeutic therapy for patients with rheumatoid arthritis (RA). However, T cell mediated arthritis relapses in patients with RA might be controlled by anti-IL-23p19 treatment.

Show MeSH

Related in: MedlinePlus

Administration of anti-IL-23p19 before onset prevents full-blown CIA.(A) DBA/1 mice were immunized with CII/CFA and three weeks later mice received a booster-injection. On days 15, 22 and 29 either anti-IL-23p19 (filled squares) or control antibody (open circles) was given intra-peritoneally. Macroscopic score (+SEM) and the average macroscopic score (average macroscopic score per individual mouse of all time points assessed, assessed by student t-test) of n = 20 mice per group from 2 independent experiments is shown, as well as the incidence.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585376&req=5

pone-0057553-g002: Administration of anti-IL-23p19 before onset prevents full-blown CIA.(A) DBA/1 mice were immunized with CII/CFA and three weeks later mice received a booster-injection. On days 15, 22 and 29 either anti-IL-23p19 (filled squares) or control antibody (open circles) was given intra-peritoneally. Macroscopic score (+SEM) and the average macroscopic score (average macroscopic score per individual mouse of all time points assessed, assessed by student t-test) of n = 20 mice per group from 2 independent experiments is shown, as well as the incidence.

Mentions: To investigate the role of IL-23 during different stages of CIA, CII/CFA-immunized DBA/1 mice were randomly separated into two groups and treated with a murine anti-murine IL-23p19 antibody or isotype control antibody at days 15, 22 and 29 p.i. At day 21 p.i., a booster-injection was given according to our CIA protocol. Significantly less severe CIA developed in the anti-IL-23p19 treated group compared to control as assessed by the arthritis score and statistically tested at each individual time point over time by using the area under the curve (AUC), and histologically (Figure 2A,B). The disease incidence was not significantly different between the two groups and no difference in the day of onset was observed (Figure 2A).


IL-23 dependent and independent stages of experimental arthritis: no clinical effect of therapeutic IL-23p19 inhibition in collagen-induced arthritis.

Cornelissen F, Asmawidjaja PS, Mus AM, Corneth O, Kikly K, Lubberts E - PLoS ONE (2013)

Administration of anti-IL-23p19 before onset prevents full-blown CIA.(A) DBA/1 mice were immunized with CII/CFA and three weeks later mice received a booster-injection. On days 15, 22 and 29 either anti-IL-23p19 (filled squares) or control antibody (open circles) was given intra-peritoneally. Macroscopic score (+SEM) and the average macroscopic score (average macroscopic score per individual mouse of all time points assessed, assessed by student t-test) of n = 20 mice per group from 2 independent experiments is shown, as well as the incidence.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585376&req=5

pone-0057553-g002: Administration of anti-IL-23p19 before onset prevents full-blown CIA.(A) DBA/1 mice were immunized with CII/CFA and three weeks later mice received a booster-injection. On days 15, 22 and 29 either anti-IL-23p19 (filled squares) or control antibody (open circles) was given intra-peritoneally. Macroscopic score (+SEM) and the average macroscopic score (average macroscopic score per individual mouse of all time points assessed, assessed by student t-test) of n = 20 mice per group from 2 independent experiments is shown, as well as the incidence.
Mentions: To investigate the role of IL-23 during different stages of CIA, CII/CFA-immunized DBA/1 mice were randomly separated into two groups and treated with a murine anti-murine IL-23p19 antibody or isotype control antibody at days 15, 22 and 29 p.i. At day 21 p.i., a booster-injection was given according to our CIA protocol. Significantly less severe CIA developed in the anti-IL-23p19 treated group compared to control as assessed by the arthritis score and statistically tested at each individual time point over time by using the area under the curve (AUC), and histologically (Figure 2A,B). The disease incidence was not significantly different between the two groups and no difference in the day of onset was observed (Figure 2A).

Bottom Line: Neutralizing IL-23 after onset of CIA in rats has been shown to reduce paw volume, but the effect on synovial inflammation and the immunological autoimmune response is not clear.Importantly, neutralizing IL-23 after the first signs of CIA did not ameliorate the disease.These data suggest that specific neutralization of IL-23p19 after onset of autoimmune arthritis may not be beneficial as a therapeutic therapy for patients with rheumatoid arthritis (RA).

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.

ABSTRACT
IL-23p19 deficient mice have revealed a critical role of IL-23 in the development of experimental autoimmune diseases, such as collagen-induced arthritis (CIA). Neutralizing IL-23 after onset of CIA in rats has been shown to reduce paw volume, but the effect on synovial inflammation and the immunological autoimmune response is not clear. In this study, we examined the role of IL-23 at different stages of CIA and during T cell memory mediated flare-up arthritis with focus on changes in B cell activity and Th1/Th17 modulation. Anti-IL-23p19 antibody (anti-IL23p19) treatment, starting 15 days after the type II collagen (CII)-immunization but before clinical signs of disease onset, significantly suppressed the severity of CIA. This was accompanied with significantly lower CII-specific IgG1 levels and lower IgG2a levels in the anti-IL-23p19 treated mice compared to the control group. Importantly, neutralizing IL-23 after the first signs of CIA did not ameliorate the disease. This was in contrast to arthritic mice that underwent an arthritis flare-up since a significantly lower disease score was observed in the IL-23p19 treated mice compared to the control group, accompanied by lower synovial IL-17A and IL-22 expression in the knee joints of these mice. These data show IL-23-dependent and IL-23-independent stages during autoimmune CIA. Furthermore, the memory T cell mediated flare-up arthritis is IL-23-mediated. These data suggest that specific neutralization of IL-23p19 after onset of autoimmune arthritis may not be beneficial as a therapeutic therapy for patients with rheumatoid arthritis (RA). However, T cell mediated arthritis relapses in patients with RA might be controlled by anti-IL-23p19 treatment.

Show MeSH
Related in: MedlinePlus