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A method is described to detect and to quantitate inflammation in knee-joints of mice. Approximately 10 muCi 99mTechnetium pertechnetate (99mTc) is injected subcutaneously in the neck region and the accumulation of the short-lived isotope in the knee-joint is detected by external gamma counting. 99mTc-uptake values correlate well with histological grading of joint inflammation at various intervals after induction of the inflammation. The method can be used to detect changes in activity of unilateral as well as bilateral joint inflammation using either the ratio of 99mTc uptake in the right knee versus that in the left knee or absolute 99mTc-uptake values.

Intravenous (i.v.) administration of 300 micrograms methylated BSA (mBSA) to C57-Black mice with unilateral antigen-induced arthritis (AIA) of 4-6 weeks duration resulted in a reproducible flare-up of ongoing arthritis without signs of inflammation in the contralateral non-arthritic knee joint. In the present study we investigated characteristics of the flare-up phenomenon using histological grading and 99mtechnetium pertechnetate uptake measurements to detect and quantitate knee joint inflammation. At 6 h after intravenous mBSA administration flare-up of arthritis was demonstrable, showing histological characteristics of acute joint inflammation; later this progressed to chronic stages, but the inflammatory stage did not return to baseline values up to day 9 after i.v. challenge. Varying the dose of i.v. mBSA from 2 to 1000 micrograms showed that 10 micrograms was sufficient to elicit the phenomenon and also that the latter is dose-dependent. Using mice immunized with both mBSA and methylated HGG (mHGG) with either mBSA or mHGG-induced arthritis, we could show that 4-6 weeks after arthritis induction the flare-up phenomenon is antigen specific. Intra-articular injection of as little as 10 ng of mBSA resulted in exacerbation of inflammation in joints with chronic mBSA-induced arthritis, but induced no inflammation in the contralateral non-arthritic knee joints, indicating local hypersensitivity in the former joints. The flare-up phenomenon may be due to local hyper-reactivity of chronically inflamed joints to minimal amounts of circulating antigen entering the joint.