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

Decreased production of anti-CII antibodies in mice treated with anti-IL-23p19.At day 35, at the end of the experiment as shown in Figure 2A, serum was collected and anti-CII antibody levels of the IgG1, IgG2a and IgG2b subclasses were determined in sera. Data are shown for each individual mouse or as the mean +SEM of n = 10 mice per group and *P<0.05; **P<0.01; ***P<0.001 as calculated by Mann-Whitney U test.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585376&req=5

pone-0057553-g003: Decreased production of anti-CII antibodies in mice treated with anti-IL-23p19.At day 35, at the end of the experiment as shown in Figure 2A, serum was collected and anti-CII antibody levels of the IgG1, IgG2a and IgG2b subclasses were determined in sera. Data are shown for each individual mouse or as the mean +SEM of n = 10 mice per group and *P<0.05; **P<0.01; ***P<0.001 as calculated by Mann-Whitney U test.

Mentions: To determine the effect of anti-IL-23p19 treatment on auto-antibody production, serum was collected at day 35 and anti-CII-specific IgG antibodies were measured. As shown in Figure 3, IgG1 levels were significantly lower in the anti-IL-23p19 treated group compared to controls. Additionally, IgG2a and IgG2b levels were lower; however, no statistically significant difference was reached.


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)

Decreased production of anti-CII antibodies in mice treated with anti-IL-23p19.At day 35, at the end of the experiment as shown in Figure 2A, serum was collected and anti-CII antibody levels of the IgG1, IgG2a and IgG2b subclasses were determined in sera. Data are shown for each individual mouse or as the mean +SEM of n = 10 mice per group and *P<0.05; **P<0.01; ***P<0.001 as calculated by Mann-Whitney U test.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057553-g003: Decreased production of anti-CII antibodies in mice treated with anti-IL-23p19.At day 35, at the end of the experiment as shown in Figure 2A, serum was collected and anti-CII antibody levels of the IgG1, IgG2a and IgG2b subclasses were determined in sera. Data are shown for each individual mouse or as the mean +SEM of n = 10 mice per group and *P<0.05; **P<0.01; ***P<0.001 as calculated by Mann-Whitney U test.
Mentions: To determine the effect of anti-IL-23p19 treatment on auto-antibody production, serum was collected at day 35 and anti-CII-specific IgG antibodies were measured. As shown in Figure 3, IgG1 levels were significantly lower in the anti-IL-23p19 treated group compared to controls. Additionally, IgG2a and IgG2b levels were lower; however, no statistically significant difference was reached.

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