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.