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The effect of a variety of antiinflammatory and antirheumatic agents on both developing and established lesions of type I1 collagen induced polyarthritis in rats was examined. Administration of the nonsteroidal antiinflammatory agents indomethacin or phenylbutazone suppressed the paw inflammation associated with the disease without affecting type I1 collagen antibody titers. Radiographic analysis of the joints showed suppression of several parameters related to joint destruction. This was most probably related to the antiinflammatory properties of the two drugs. Administration of prednisolone, a steroidal antiinflammatory agent, suppressed paw inflammation; type 11 collagen antibody titers were significantly decreased in the developing lesion, but the drug had no effect on antibody titers in the established lesion. Radiographic analysis of the joints showed decreases in several parameters of joint destruction. Cyclophosphamide, an immunosuppressive agent, completely suppressed the inflammation associated with the developing lesion but had only minimal effect against the established disease. Collagen antibody titers were decreased and an improvement in only one radiologic parameter (periostitis) was detected. Treatment with antirheumatic agents such as gold thioglucose or levamisole enhanced severity of inflam- Submitted for publication April 30, 1980; accepted in revised form October 7, 1980. mation in the established lesion and caused increases in collagen antibody titers. Radiographic analysis of the joints indicated that while gold had no effect, levamisole enhanced joint destruction. Treatment with D-penicillamine had no effect on paw inflammation, despite increases in collagen antibody titers. Radiographic analysis of the joints indicated an improvement in all parameters related to joint destruction in animals treated with penicillamine.The demonstration of antibodies to collagen in the sera and synovial fluids of patients with rheumatoid arthritis (1-8) has led to the view that immunologic hypersensitivity to collagen may, at least in part, contribute to the inflammation and joint destruction that is observed in the disease. Supporting this view, several studies (9;13) have shown that when native cartilage specific type I1 collagen (homologous or heterologous) in an oil emulsion was injected intradermally into rats, approximately 40% of the animals developed an inflammatory polyarthritis. Denatured type I1 collagen or the other genetically distinct forms such as type I, 111, and IV did not elicit this response. Passive transfer of the polyarthritis in rats was also achieved by the administration of sensitized lymph node and spleen cells, again suggesting that the polyarthritis observed in these animals was related, at least in part, to immunologic hypersensitivity to type I1 collagen (14).Although the relationship of this animal model to human disease is not established, several similarities exist between the two lesions. Both lesions contain mononuclear cell infiltrates in the synovial tissue and begin...

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The effect of cobra venom factor on the developing and the established lesion of collagen-induced rat polyarthritis has been examined. In the developing lesion, decomplementation by cobra venom factor results in a delay in the onset of inflammation and a decrease in the radiological parameters of joint destruction. Under the conditions of the decomplementation, antibody titers to collagen are not decreased. In the established lesion, treatment with cobra venom factor has no effect, on either the inflammatory lesion or the various radiological parameters of joint destruction.

Fenbufen [3-(4-biphenylylcarbonyl)propionic acid] was shown to be an orally and parenterally effective nonsteroidal antiinflammatory analgetic and antipyretic agent in animals. Like clinically useful drugs (aspirin, phenylbutazine and indomethacin) it has potent antiinflammatory activity in a wide spectrum of laboratory tests in mice, rats, guinea pigs, and dogs and was of particular interest since it appears to have high analgetic efficacy and a long duration of antiinflammatory and analgetic action. While shown to have ulcerogenic potential in rats at toxic doses, it appeared to have a superior margin of gastrointestinal safety in treatment of dogs with urate synovitis. Evidence was also presented to show that BPAA (4-biphenylacetic acid), a metabolite of fenbufen, has a similar profile of antiinflammatory activity, although appearing to produce slightly more gastrointestinal injury. It appears that BPAA may be the agent responsible for at least part of fenbufen's pharmacologic effects. The data presented suggest that fenbufen has the potential to be used safely and effectively to provide relief for patients with inflammatory disease.