TREATMENT OF RAT ARTHRITIDES WITH CLODRONATE-CONTAINING LIPOSOMES

Large multilamellar liposomes containing dichloro-methylene-bisphospho nate (clodronate; Clo), a bisphosphonate that becomes toxic when intra cellularly concentrated, were used to therapeutically target macrophag es (M phi) in rats with established adjuvant arthritis (AA; i.v. on da ys 10,11,12) or antigen-induced arthritis (AIA; i.v. or i.a. on 3 h, d ays 1,2). In established AA, i.v. injection of Clo-liposomes led to si gnificant, long-lasting amelioration of clinical parameters, and to re duced destruction of the ankle joint even several weeks after terminat ion of treatment. In the acute phase of established AIA, intravenous t reatment induced transient clinical amelioration, but did not countera ct joint destruction. I.a. treatment in AIA was ineffective. Systemic treatment with anti-M phi principles induces amelioration of both AA a nd AIA; the improvement appears more profound in AA, i.e., the model w ith a more systemic character. Preliminary data indicate that depletio n of M phi occurs in the liver rather than in spleen, draining lymph n odes or synovial membrane. In addition, local treatment with the same principle is ineffective in AIA. Therefore, systemic elimination of M phi in different sites may be crucial for effective therapy of arthrit is with anti-M phi agents.