A trial of clodronate-liposomes as
anti-macrophage treatment in a sheep model of arthritis
J. Highton1, D. Guevremont1, J. Thomson1, B. Carlisle2,
I. Tucker3
Department of Medicine1, University of Otago Medical School; Department of
Biochemistry2; School of Pharmacy3, University of Otago, Dunedin,
New Zealand.
ABSTRACT
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 anti-macrophage 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.
Key words
Clodronate-liposomes, treatment of arthritis, sheep model of arthritis.
J. Highton, MD FRACP, Associate Professor; D.
Guevremont, BSc, Junior Research Fellow; J. Thomson, BSc, Research Assistant; B. Carlisle,
BSc Hons., Junior Research Fellow; Ian Tucker, Professor, School of Pharmacy.
This work was supported by grants from the Health Research Council of New Zealand and the
Otago Medical Research Foundation.
Please address correspondence and reprint requests to: Dr. J. Highton, Department of
Medicine, University of Otago School of Medicine, P.O. Box 913, Dunedin, New Zealand.
Received on March 3, 1997; accepted in revised form on August 10, 1998.
Clin Exp Rheumatol 1999; 17: 43-48.
© Copyright Clinical and Experimental
Rheumatology 1999.