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Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat

BACKGROUND: To facilitate the development of therapies for rheumatoid arthritis (RA), the Innovative Medicines Initiative BTCure has combined the experience from several laboratories worldwide to establish a series of protocols for different animal models of arthritis that reflect the pathogenesis o...

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Autores principales: Tuncel, Jonatan, Haag, Sabrina, Hoffmann, Markus H., Yau, Anthony C. Y., Hultqvist, Malin, Olofsson, Peter, Bäcklund, Johan, Nandakumar, Kutty Selva, Weidner, Daniela, Fischer, Anita, Leichsenring, Anna, Lange, Franziska, Haase, Claus, Lu, Shemin, Gulko, Percio S., Steiner, Günter, Holmdahl, Rikard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881957/
https://www.ncbi.nlm.nih.gov/pubmed/27227821
http://dx.doi.org/10.1371/journal.pone.0155936
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author Tuncel, Jonatan
Haag, Sabrina
Hoffmann, Markus H.
Yau, Anthony C. Y.
Hultqvist, Malin
Olofsson, Peter
Bäcklund, Johan
Nandakumar, Kutty Selva
Weidner, Daniela
Fischer, Anita
Leichsenring, Anna
Lange, Franziska
Haase, Claus
Lu, Shemin
Gulko, Percio S.
Steiner, Günter
Holmdahl, Rikard
author_facet Tuncel, Jonatan
Haag, Sabrina
Hoffmann, Markus H.
Yau, Anthony C. Y.
Hultqvist, Malin
Olofsson, Peter
Bäcklund, Johan
Nandakumar, Kutty Selva
Weidner, Daniela
Fischer, Anita
Leichsenring, Anna
Lange, Franziska
Haase, Claus
Lu, Shemin
Gulko, Percio S.
Steiner, Günter
Holmdahl, Rikard
author_sort Tuncel, Jonatan
collection PubMed
description BACKGROUND: To facilitate the development of therapies for rheumatoid arthritis (RA), the Innovative Medicines Initiative BTCure has combined the experience from several laboratories worldwide to establish a series of protocols for different animal models of arthritis that reflect the pathogenesis of RA. Here, we describe chronic pristane-induced arthritis (PIA) model in DA rats, and provide detailed instructions to set up and evaluate the model and for reporting data. METHODS: We optimized dose of pristane and immunization procedures and determined the effect of age, gender, and housing conditions. We further assessed cage-effects, reproducibility, and frequency of chronic arthritis, disease markers, and efficacy of standard and novel therapies. RESULTS: Out of 271 rats, 99.6% developed arthritis after pristane-administration. Mean values for day of onset, day of maximum arthritis severity and maximum clinical scores were 11.8±2.0 days, 20.3±5.1 days and 34.2±11 points on a 60-point scale, respectively. The mean frequency of chronic arthritis was 86% but approached 100% in long-term experiments over 110 days. Pristane was arthritogenic even at 5 microliters dose but needed to be administrated intradermally to induce robust disease with minimal variation. The development of arthritis was age-dependent but independent of gender and whether the rats were housed in conventional or barrier facilities. PIA correlated well with weight loss and acute phase reactants, and was ameliorated by etanercept, dexamethasone, cyclosporine A and fingolimod treatment. CONCLUSIONS: PIA has high incidence and excellent reproducibility. The chronic relapsing-remitting disease and limited systemic manifestations make it more suitable than adjuvant arthritis for long-term studies of joint-inflammation and screening and validation of new therapeutics.
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spelling pubmed-48819572016-06-10 Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat Tuncel, Jonatan Haag, Sabrina Hoffmann, Markus H. Yau, Anthony C. Y. Hultqvist, Malin Olofsson, Peter Bäcklund, Johan Nandakumar, Kutty Selva Weidner, Daniela Fischer, Anita Leichsenring, Anna Lange, Franziska Haase, Claus Lu, Shemin Gulko, Percio S. Steiner, Günter Holmdahl, Rikard PLoS One Research Article BACKGROUND: To facilitate the development of therapies for rheumatoid arthritis (RA), the Innovative Medicines Initiative BTCure has combined the experience from several laboratories worldwide to establish a series of protocols for different animal models of arthritis that reflect the pathogenesis of RA. Here, we describe chronic pristane-induced arthritis (PIA) model in DA rats, and provide detailed instructions to set up and evaluate the model and for reporting data. METHODS: We optimized dose of pristane and immunization procedures and determined the effect of age, gender, and housing conditions. We further assessed cage-effects, reproducibility, and frequency of chronic arthritis, disease markers, and efficacy of standard and novel therapies. RESULTS: Out of 271 rats, 99.6% developed arthritis after pristane-administration. Mean values for day of onset, day of maximum arthritis severity and maximum clinical scores were 11.8±2.0 days, 20.3±5.1 days and 34.2±11 points on a 60-point scale, respectively. The mean frequency of chronic arthritis was 86% but approached 100% in long-term experiments over 110 days. Pristane was arthritogenic even at 5 microliters dose but needed to be administrated intradermally to induce robust disease with minimal variation. The development of arthritis was age-dependent but independent of gender and whether the rats were housed in conventional or barrier facilities. PIA correlated well with weight loss and acute phase reactants, and was ameliorated by etanercept, dexamethasone, cyclosporine A and fingolimod treatment. CONCLUSIONS: PIA has high incidence and excellent reproducibility. The chronic relapsing-remitting disease and limited systemic manifestations make it more suitable than adjuvant arthritis for long-term studies of joint-inflammation and screening and validation of new therapeutics. Public Library of Science 2016-05-26 /pmc/articles/PMC4881957/ /pubmed/27227821 http://dx.doi.org/10.1371/journal.pone.0155936 Text en © 2016 Tuncel et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Tuncel, Jonatan
Haag, Sabrina
Hoffmann, Markus H.
Yau, Anthony C. Y.
Hultqvist, Malin
Olofsson, Peter
Bäcklund, Johan
Nandakumar, Kutty Selva
Weidner, Daniela
Fischer, Anita
Leichsenring, Anna
Lange, Franziska
Haase, Claus
Lu, Shemin
Gulko, Percio S.
Steiner, Günter
Holmdahl, Rikard
Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat
title Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat
title_full Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat
title_fullStr Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat
title_full_unstemmed Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat
title_short Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat
title_sort animal models of rheumatoid arthritis (i): pristane-induced arthritis in the rat
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881957/
https://www.ncbi.nlm.nih.gov/pubmed/27227821
http://dx.doi.org/10.1371/journal.pone.0155936
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