Establishment of a sustained delayed type hypersensitivity model with mono-arthritic manifestations in C57Bl/6J mice (101.17)

Abstract

Abstract RA is a progressive, inflammatory and destructive autoimmune disease, characterized by chronic synovial joint inflammation. Various RA models of both mono-and polyarthritis have been developed in different inbred strains of mice. However, establishment of sustained arthritis models in the C57Bl/6J mice has been difficult. As most genetically modified mice are bred on the C57Bl/6J background, there is a need to explore new approaches of obtaining robust models in this mouse strain. We have established a sustained DTH model with monoarthritic manifestations in C57Bl/6J mice. The model builds on a classical transient DTH model, where a DTH reaction is elicited by antigen injection into the right hind footpad at 7 day post Antigen sensitisation. Interestingly, we find that administration of a single low dose of a monoclonal antibody cocktail of anti-collagen type II antibodies before elicitation of the DTH reaction results in a sustained footpad swelling that is maintained for at least two weeks. Histopathological examination revealed inflammation and bone destruction with characteristics of arthritis with only the Antigen challenged footpad being affected (monoarthritis). This was not observed in mice receiving an isotype antibody cocktail. Moreover, no mice receiving anti-CII antibodies alone developed polyarthritis. Similar results were obtained using Balb/C mice thus the presence of anti-CII antibodies appears crucial for development of sustained joint tissue inflammation.