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.