Anti-adjuvant arthritis of recombinant human endostatin in rats via inhibition of angiogenesis and proinflammatory factors

• Published in: Acta pharmacologica Sinica Vol. 25; no. 9; p. 1182
• Main Authors: Yue, Li, Wang, Hua, Liu, Li-Hua, Shen, Yu-Xian, Wei, Wei
• Format: Journal Article
• Language: English
• Published: United States 01.09.2004
• Subjects: Angiogenesis Inhibitors - pharmacology; Animals; Arthritis, Experimental - chemically induced; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Endostatins - pharmacology; Freund's Adjuvant; Interleukin-1 - metabolism; Interleukin-2 - metabolism; Macrophages, Peritoneal - metabolism; Male; Rats; Rats, Sprague-Dawley; Recombinant Proteins - pharmacology; Synovial Membrane - metabolism; Synovial Membrane - pathology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1671-4083

To investigate the profile of endostatin on adjuvant arthritis (AA) and angiogenesis blockade in synovitis. The model of rat AA was induced by injection of intradermal complete Freund's adjuvant (CFA). Hind paw volume of rat was measured by volume meter and the activities of interleukin-1 (IL-1) and IL-2 were measured by the assay of thymocytes proliferation. IL-1beta and tumor necrosis factor-alpha (TNF-alpha) produced by synoviocytes was estimated with radioimmunoassay. The number of new blood vessels in knee joint synovium was counted under microscope by hematoxylin and eosin (HE) staining. The secondary inflammation of AA rats appeared on the 10th day after injection of CFA. The therapeutic administration of endostatin (0.1, 0.5, and 2.5 mg/kg/d, sc, plus 7 d) was given from that time (d 10). It was found that endostatin significantly inhibited the secondary paw swelling and the number of new blood vessels in the synovium of AA rats. Endostatin significantly decreased the production of IL-1 derived from both peritoneal macrophages and synoviocytes and IL-2 from splenocytes, especially at the dose of 2.5 mg/kg. This effect of endostatin also was seen on TNF-alpha produced by synoviocytes. The recombinant human endostatin had an inhibitory effect on rat AA, which was related to its anti-angiogenesis and inhibition of proinflammatory cytokines.