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

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

Tuncel, J. (author): Harvard Medical School, Boston, Massachusetts, United States of America; Karolinska Institutet, Stockholm, Sweden

Haag, S. (author): Karolinska Institutet, Stockholm, Sweden

Hoffmann, M. H. (author): University of Erlangen-Nuremberg, Erlangen, Germany; Medical University of Vienna, Vienna, Austria,Redoxis AB, Medicon Village, Lund, Sweden

Yau, A. C. (author): Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden

Hultqvist, M. (author): Redoxis AB, Medicon Village, Lund, Sweden

Olofsson, P. (author): Redoxis AB, Medicon Village, Lund, Sweden

Bäcklund, J. (author): Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden

Nandakumar, Kutty Selva, 1965- (author): Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden

Weidner, D. (author): University of Erlangen-Nuremberg, Erlangen, Germany

Fischer, A. (author): Medical University of Vienna, Vienna, Austria

Leichsenring, A. (author): Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

Lange, F. (author): Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

Haase, C. (author): Novo Nordisk A/S, Malov, Denmark

Lu, S. (author): Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR China

Gulko, P. S. (author): Icahn School of Medicine at Mount Sinai, New York, New York, United States of America,Medical University of Vienna, Vienna, Austria

Steiner, G. (author): Medical University of Vienna, Vienna, Austria

Holmdahl, R. (author): Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden

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(creator_code:org_t)

2016-05-26
2016
English.
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5

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Journal article (peer-reviewed)

Abstract Subject headings

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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Keyword

Animals
Arthritis
Experimental/*chemically induced/*pathology
Arthritis
Rheumatoid/*chemically induced/*pathology
*Disease Models
Animal
Female
Immunosuppressive Agents/*toxicity
Male
Rats
Terpenes/*toxicity

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor: Tuncel, J.; Haag, S.; Hoffmann, M. H.; Yau, A. C.; Hultqvist, M.; Olofsson, P.; show more...; Bäcklund, J.; Nandakumar, Kutt ...; Weidner, D.; Fischer, A.; Leichsenring, A.; Lange, F.; Haase, C.; Lu, S.; Gulko, P. S.; Steiner, G.; Holmdahl, R.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

Articles in the publication: PLOS ONE

By the university: Halmstad University; Karolinska Institutet

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