title: IL-23 dependent and independent stages of experimental arthritis: no clinical effect of therapeutic IL-23p19 inhibition in collagen-induced arthritis.
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.
authors.affiliation: Department of Rheumatology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Ferry
authors.initials: F
authors.lastname: Cornelissen
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Asmawidjaja
authors.forename: Adriana M C
authors.initials: AM
authors.lastname: Mus
authors.forename: Odilia
authors.initials: O
authors.lastname: Corneth
authors.forename: Kristine
authors.initials: K
authors.lastname: Kikly
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003094:Collagen / Q000633:toxicity*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007156:Immunologic Memory; D053759:Interleukin-23 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D053759:Interleukin-23; D003094:Collagen