Head-to-Head Comparison of Protocol Modifications for the Generation of Collagen-Induced Arthritis in a Specific-Pathogen Free Facility Using DBA/1 Mice

Abstract

Collagen-induced arthritis (CIA) is a widely used mouse model for studying inflammatory arthritis (IA). However, CIA induction protocols differ between laboratories, and direct comparison between protocol variations has not been reported. To address this issue, DBA/1 mice housed in conventional and specific-pathogen free (SPF) facilities were administered various combinations of two doses of collagen type II (CII) in complete (CFA) or incomplete Freund's adjuvant (IFA); some mice were also injected with lipopolysaccharide (LPS) and/or additional CII at specific intervals. Mice were evaluated for IA over the subsequent 2 months. Depending directly on the combination of CII, CFA, IFA, and LPS used, the incidence of IA ranged between 20%-100%, and severity extended from mild to severe even in an SPF environment. Our results demonstrate for the first time in head-to-head comparisons that specific variations in the use of CII, CFA, IFA, and LPS can induce a range of arthritic disease intensity and severity in an SPF facility. Thus, distinct experimental settings can be designed for robust assessment of factors that either exacerbate or inhibit arthritis pathogenesis. Furthermore, by achieving 100% incidence in an SPF facility, the protocols provide a practical and humane benefit by reducing the number of mice necessary for experimental assessment.

Refinement and validation of infrared thermal imaging (IRT): a non-invasive technique to measure disease activity in a mouse model of rheumatoid arthritis

“…Arthritis induction was done by intradermal injection of an emulsion consisting of bovine type II collagen in complete Freund's adjuvant (CFA), followed 21 days later by a booster immunization with type II collagen emulsified in incomplete Freund's adjuvant (IFA). On day 25, to synchronize onset of arthritis, 2 mg/kg lipopolysaccharides (LPS) from Escherichia coli O111:B4 (Sigma) in 100 μL saline was injected intraperitoneally to synergistically trigger and enhance arthritis [37].…”

A Review on Complete Freund’s Adjuvant-Induced Arthritic Rat Model: Factors Leading to its Success

“…Adjuvants have been applied to boost the immune responses of the animal host to an antigen since more than 70 years ago. 1 The adjuvants include collagen type I or II, lipopolysaccharides, carrageenan, complete or incomplete Freund's adjuvant, formalin, pristine, squalene, and 6-sulfanilamidoindazole [2][3][4][5][6] generally produce arthritogenic signals depending on types of adjuvants used and immunisation procedures using specific antigens to cause a self-tolerance breakdown. 7 Adjuvant-induced arthritis (AIA) model has been extensively developed to mimic certain conditions of human diseases, especially arthritis.…”

“…AIA model develops mechanical allodynia, thermal hyperalgesia, flare pain following joint movement (joint hyperalgesia), reduced mobility, and increased swelling indicating oedema formation and joint stiffness. [2][3][4][8][9] Amongst AIA models, CFA-induced arthritis seems the most reliable 5,7 and justifiable in research. 11 CFA is arthritis was later identified due to the sole action of the CFA-mycobacterial component.…”