1. Suppression of chronic streptococcal cell wall-induced arthritis in Lewis rats by liposomal clodronate.
- Author
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Richards PJ, Williams BD, and Williams AS
- Subjects
- Animals, Ankle Joint metabolism, Ankle Joint pathology, Arthritis, Experimental pathology, Clodronic Acid administration & dosage, Disease Models, Animal, Drug Carriers, Female, Image Processing, Computer-Assisted, Immunoenzyme Techniques, Injections, Intravenous, Interleukin-1 metabolism, Interleukin-6 metabolism, Liposomes, Macrophages drug effects, Macrophages pathology, Matrix Metalloproteinase 9 metabolism, Rats, Rats, Inbred Lew, Tumor Necrosis Factor-alpha metabolism, Arthritis, Experimental drug therapy, Clodronic Acid therapeutic use
- Abstract
Objectives: 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.
- Published
- 2001
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