A trial of clodronate-liposomes as anti-macrophage treatment in a sheep model of arthritis.

OBJECTIVE

Our previous research has concerned the role of macrophages in joint inflammation in rheumatoid arthritis. We have therefore been interested in liposomes containing clodronate as an antimacrophage treatment for arthritis. We have used the antigen-induced arthritis model in sheep to evaluate the effect of clodronate liposomes.

METHODS

Arthritis was induced in the right hock joint (day 0). We were able to demonstrate uptake of liposomes into macrophages within the inflamed joint lining. On day 7, sheep were given a single intra-articular injection of clodronate liposomes (group 1, n = 10) or saline liposomes (group 2, n = 10). A further 6 sheep (group 3) had no arthritis and no treatment.

RESULTS

No difference in joint diameter was observed between the sheep in group 1 (clodronate) and group 2 (saline treated). Both groups had joint swelling which persisted until the end of the trial (day 20). Histologic scoring was also similar in group 1 and group 2 animals, and both were worse than group 3.

CONCLUSION

In vitro studies have shown that interaction of liposomes with neutrophils and monocytes stimulates a respiratory burst. Despite this possible pro-inflammatory effect we did not observe any increase in joint diameter following liposome injection. Thus we were unable to demonstrate a therapeutic effect of a single dose of clodronate liposomes in this large animal model of antigen-induced arthritis.