Development of a delayed-type hypersensitivity granuloma model in the mouse for the study of chronic immune-mediated inflammatory disease

A cutaneous model of delayed-type hypersensitivity granuloma (DTH GRA) was developed, using methylated bovine serum albumin (mBSA) which could be easily quantified and represented chronic cellular immune-mediated inflammation characteristic of rheumatoid arthritis (RA). Quantitative kinetics showed maximal DTH GRA wet tissue weights at d. 5 post-induction, diminishing between d. 15–22; DTH GRA dry tissue weights peaked between d. 8–22. Histological evaluation revealed early extensive fibrin deposition, edema, mixed PMN/mononuclear leucocyte infiltration and angiogenesis (d. 2–5), followed by increased macrophage recruitment, lymphocyte infiltration, angiogenesis and vasculitis (d. 10–15). Fibrin resorption and replacement by fibrous tissue resulted in resolution by d. 35. It is suggested that the DTH GRA reaction represents a relevant model for probing pathogenic mechanisms and potential therapeutics for RA.