title: Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Tuncel
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Haag
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.|Division of Rheumatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Hoffmann
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anthony C Y
authors.initials: AC
authors.lastname: Yau
authors.affiliation: Redoxis AB, Medicon Village, Lund, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Hultqvist
authors.affiliation: Redoxis AB, Medicon Village, Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Olofsson
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Bäcklund
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kutty Selva
authors.initials: KS
authors.lastname: Nandakumar
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Weidner
authors.affiliation: Division of Rheumatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Anita
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Leichsenring
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Lange
authors.affiliation: Department of Immunopharmacology, Novo Nordisk A/S, Malov, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Haase
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR China.
authors.forename: Shemin
authors.initials: S
authors.lastname: Lu
authors.affiliation: Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Percio S
authors.initials: PS
authors.lastname: Gulko
authors.affiliation: Division of Rheumatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Steiner
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008297:Male; D051381:Rats; D013729:Terpenes / Q000633:toxicity*
chemical_list: D007166:Immunosuppressive Agents; D013729:Terpenes; C009042:pristane