Anti-adjuvant arthritis of recombinant human endostatin in rats via inhibition of angiogenesis and proinflammatory factors.
OBJECTIVE
To investigate the profile of endostatin on adjuvant arthritis (AA) and angiogenesis blockade in synovitis.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The recombinant human endostatin had an inhibitory effect on rat AA, which was related to its anti-angiogenesis and inhibition of proinflammatory cytokines.
Yue
Li
L
Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China.
Wang
Hua
H
Liu
Li-Hua
LH
Shen
Yu-Xian
YX
Wei
Wei
W
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D043169:Endostatins / Q000494:pharmacology*; D005620:Freund's Adjuvant; D007375:Interleukin-1 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005620:Freund's Adjuvant