Pharmacological Value of Murine Delayed‐type Hypersensitivity Arthritis: A Robust Mouse Model of Rheumatoid Arthritis in C57BL/6 Mice

Abstract

In this MiniReview, we summarize the body of knowledge on the delayed-type hypersensitivity arthritis (DTHA) model, a recently developed arthritis model with 100% incidence, low variation and synchronized onset in C57BL/6 (B6) mice, and compare it to other murine arthritis models. It is desirable to have robust arthritis models in B6 mice, as many transgene strains are bred on this background. However, several of the most widely used mouse model of arthritis cannot be induced in B6 mice without the drawback of lower incidence, reduced severity and higher variation, if at all. DTHA is induced by modifying a classical methylated bovine serum albumin (mBSA)-induced DTH response by administering a cocktail of anti-type II collagen antibodies (anti-CII) between immunization and challenge. Arthritis affects one, predefined paw in which acute inflammation and severe arthritis rapidly develop and peak after 4-7 days. Disease is self-resolving over the course of around 3 weeks. Disease manifestations resemble those seen in other arthritis models and include bone erosion, cartilage destruction, oedema, pannus and new bone formation. Induction of DTHA is dependent on CD4 + T cells while B cells are dispensable. The DTHA model is set apart from other murine arthritis models in that it can be induced in B6 mice with 100% incidence and with high and consistent severity. This is the clearest advantage of the model, as the mechanisms of disease and clinical manifestations can be found in other arthritis models. The model holds potential for future modifications that may improve the lack of chronicity.

Tanshinone IIA Suppresses Proliferation and Inflammatory Cytokine Production of Synovial Fibroblasts from Rheumatoid Arthritis Patients Induced by TNF-α and Attenuates the Inflammatory Response in AIA Mice

“…To highlight the potential of Tan IIA for RA treatment, we first used an AIA mouse model to verify its therapeutic effects. The AIA model has been widely used to clarify the pathogenesis of RA and to explore potential therapeutic targets, including the validation of the therapeutic effects of new drugs (Sardar and Andersson, 2016;Atkinson and Nansen, 2017;Dong et al, 2019;Du et al, 2019). Our experiments showed that AIA mice treated with Tan IIA showed decreased histologic scores and attenuated synovial inflammation.…”

“…Eighteen male C57BL/6 mice, about 20 g in body weight each, were divided into three groups randomly: the normal group, AIA model group, and AIA model with Tan IIA treatment group. The protocol for inducing the AIA model was as previously described (Atkinson and Nansen, 2017;Dong et al, 2019;Du et al, 2019;Grötsch et al, 2019), adjusted on some points. The experimental timeline for AIA is shown in Figure 1.…”

Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

“…DTH arthritis model. The arthritis model was transferred to female C57BL/6 mice (30,31). As described, the mice were immunized on day 27 with methylated BSA (mBSA, A1009; Sigma, Darmstadt, Germany) in CFA (263810; BD Difco, Franklin Lakes, NJ), followed by an i.v.…”

Impact of delayed type hypersensitivity arthritis on development of heart failure by aortic constriction in mice

“…Clinical relevance in this aspect reflects the model’s pathophysiological relevance, type of immune response as well as the magnitude and duration of the inflammatory response. As previously described, the DTHA model displays a pathogenesis at least partly resembling the human counterpart [ 26 , 29 ]. The experimental arthritis phenotype is triggered by an unspecific antigen (mBSA, this resembling a neoantigen) and it generates a familiar local inflammation with systemic “spillover”.…”