The effects of orally administered calcium pentosan polysulfate on inflammation and cartilage degradation produced in rabbit joints by intraarticular injection of a hyaluronate-polylysine complex.
OBJECTIVE
To determine the antiinflammatory and cartilage-protecting activities of orally administered calcium pentosan polysulfate (CaPPS) in a rabbit model of inflammatory arthritis.


METHODS
A single intraarticular injection of a preformed polycation complex (PC) of poly-D-lysine and hyaluronan was used to induce joint inflammation; saline was injected into the contralateral joint as a control. Animals were killed 1, 4, 7, or 10 days post-PC injection. CaPPS, at 5 mg/kg, 10 mg/kg, or 75 mg/kg, was given every 48 hours commencing 7 days prior to PC injection. Serum interleukin-6 (IL-6), synovial fluid (SF) prostaglandin E2, cell numbers, and cartilage proteoglycan (PG) content, composition, and biosynthesis were determined for PC- and saline-injected joints.


RESULTS
In PC-injected, non-drug-treated animals, serum IL-6 activity, SF leukocyte numbers, and prostaglandin E2 levels were elevated, while cartilage PG content and biosynthesis were reduced. CaPPS at 10 mg/kg, but not at 5 mg/kg, decreased serum IL-6 levels but maintained cartilage PG concentration and biosynthesis. However, SF leukocyte counts and prostaglandin E2 levels (except on day 1) were not reduced.


CONCLUSIONS
The ability of CaPPS to attenuate serum IL-6 levels and preserve cartilage PGs in inflamed rabbit joints suggests that this substance could be of value as an effective orally administered chondroprotective, antiarthritic drug.
Smith
M M
MM
Raymond Purves Bone and Joint Research Laboratories, (University of Sydney), Royal North Shore Hospital, Australia.
Ghosh
P
P
Numata
Y
Y
Bansal
M K
MK
D000284:Administration, Oral; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D002357:Cartilage Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D002358:Cartilage, Articular / Q000737:chemistry; D004195:Disease Models, Animal; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D015850:Interleukin-6 / Q000097:blood; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000494:pharmacology*; D011107:Polylysine / Q000008:administration & dosage*; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D013462:Sulfur Radioisotopes; D013582:Synovial Fluid / Q000166:cytology
D015850:Interleukin-6; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; D011107:Polylysine; D010426:Pentosan Sulfuric Polyester; D006820:Hyaluronic Acid