Flare-up of antigen-induced arthritis in mice after challenge with intravenous antigen: effects of pre-treatment with cobra venom factor and anti-lymphocyte serum.

Intravenous injection of methylated bovine serum albumin (mBSA) into mice with unilateral chronic mBSA-induced arthritis (AIA) causes a flare-up of the joint inflammation without affecting the contralateral non-arthritic knee joint. We studied the mechanism of the flare-up by decomplementation with cobra venom factor (CoVF) and by treatment with anti-lymphocyte serum (ALS) prior to the induction of the flare-up. Treatment of mice with CoVF had no effect on the induction of the flare-up reaction whereas a reversed passive Arthus reaction (RPA) in the ear of similarly treated mice was clearly suppressed. The complement activity in the serum was zero at 2 h after CoVF treatment and remained for 24 h. This indicates that this type of flare-up reaction is not complement-dependent. On the other hand, the flare-up reaction was completely abolished after treatment with ALS. Control experiments revealed that ALS treatment diminished the number of lymphocytes in the peripheral blood and clearly suppressed a delayed hypersensitivity reaction in the ear, but had no effect on an RPA. These results suggest an important role of T lymphocytes in the mechanism of the flare-up of arthritis. T lymphocytes were demonstrated in the synovial tissue of chronically inflamed joints by immunofluorescence and appeared to be diminished after ALS treatment. Interaction between exogenous antigen and antigen reactive T lymphocytes present in chronically inflamed joints, may be an important principle in the exacerbation and propagation of joint inflammation.