Suppression of chronic streptococcal cell wall-induced arthritis in Lewis rats by liposomal clodronate.
OBJECTIVE
To investigate the role of macrophages in the pathogenesis of chronic streptococcal cell wall (SCW)-induced arthritis using liposomal clodronate.


METHODS
Female Lewis rats with SCW-induced arthritis received a single intravenous injection of 20 mg of clodronate encapsulated within small unilamellar vesicles (SUVc) 10 days post-arthritis induction.


RESULTS
SUVc significantly suppressed the development of chronic SCW-induced arthritis for up to 26 days after treatment. At this time point, ED1(+) macrophages were significantly depleted in the liver and ankle joints, although splenic macrophage numbers were not significantly different from control groups. Macrophage elimination induced a significant reduction in local levels of interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNFalpha) and matrix metalloproteinase-9 (MMP-9) from ankle joints.


CONCLUSIONS
Macrophage elimination by SUVc inhibits local production of IL-1beta, IL-6, TNFalpha and MMP-9, and the pathogenesis of inflammatory arthritis.
Richards
P J
PJ
Rheumatology Research Laboratory, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK.
Williams
B D
BD
Williams
A S
AS
D000818:Animals; D000843:Ankle Joint / Q000378:metabolism / Q000473:pathology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D004002:Clodronic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004337:Drug Carriers; D007375:Interleukin-1; D015850:Interleukin-6; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid; D020780:Matrix Metalloproteinase 9