Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782434048737542144 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4881957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tunceljonatan animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT haagsabrina animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT hoffmannmarkush animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT yauanthonycy animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT hultqvistmalin animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT olofssonpeter animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT backlundjohan animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT nandakumarkuttyselva animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT weidnerdaniela animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT fischeranita animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT leichsenringanna animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT langefranziska animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT haaseclaus animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT lushemin animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT gulkopercios animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT steinergunter animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat AT holmdahlrikard animalmodelsofrheumatoidarthritisipristaneinducedarthritisintherat |