Suppression of chronic streptococcal cell wall-induced arthritis in Lewis rats by liposomal clodronate.

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.

• Authors: P J Richards, B D Williams, A S Williams
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 40 Issue 9 Pg. 978-87 (Sep 2001) ISSN: 1462-0324 [Print] England
• PMID: 11561107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Carriers
• Interleukin-1
• Interleukin-6
• Liposomes
• Tumor Necrosis Factor-alpha
• Clodronic Acid
• Matrix Metalloproteinase 9

Topics

• Animals
• Ankle Joint (metabolism, pathology)
• Arthritis, Experimental (drug therapy, pathology)
• Clodronic Acid (administration & dosage, therapeutic use)
• Disease Models, Animal
• Drug Carriers
• Female
• Image Processing, Computer-Assisted
• Immunoenzyme Techniques
• Injections, Intravenous
• Interleukin-1 (metabolism)
• Interleukin-6 (metabolism)
• Liposomes
• Macrophages (drug effects, pathology)
• Matrix Metalloproteinase 9 (metabolism)
• Rats
• Rats, Inbred Lew
• Tumor Necrosis Factor-alpha (metabolism)