Specific variations in the protocol for the induction of collagen-induced arthritis in mice improve reproducibility of disease severity and incidence in an SPF facility (BA6P.136)

Abstract

Abstract Collagen-induced arthritis (CIA) is a widely used model for studying inflammatory arthritis (IA). CIA incidence and severity (I&S) varies between labs. Factors effecting induction include; adjuvant, # of collagen type II (CII) immunizations (imm), use of LPS and environmental hygiene. A better understanding of the effects of variations in protocols/environment on the I&S of CIA would improve the quality use this model. Method: Mice in conventional (con) and specific-pathogen free (SPF) facilities were compared. Mice were imm with 2 doses CII in complete (CFA) or incomplete (IFA) Freund’s adjuvant. LPS and/or CII were given at specific intervals following the 2nd imm. IA was evaluted using established scoring systems. Result: Following CII/CFA imm, con-housed had higher I&S of IA than SPF-housed mice. For SPF-housed mice, LPS 3 d after the 2nd CII/CFA imm modestly increased IA I&S. Unlike LPS or CII alone, additional LPS+CII 14 and 28 d later resulted in severe IA in all mice. Substitution of IFA for CFA along with LPS/CII at 14 and 28 d allowed for development of moderately severe IA in 80% of mice. Conclusion: Specific variations in use of CII, CFA, IFA and LPS can induce a range of IA I&S in a SPF facility . Thus, distinct experimental settings may be designed for robust assessment of factors that either exacerbate or inhibit arthritis pathogenesis. These protocols provide a practical and humane benefit of reducing cost, time and mice necessary for experimental assessment.