SummaryNeovascularization is observed in a spectrum of diseases such as solid tumors, diabetic retinopathy, and rheumatoid arthritis. It is also evident in rat collagen-induced arthritis (CIA), an animal model with histologic, clinical, and radiographic manifestations resembling rheumatoid arthritis. To evaluate the effects of angioinhibition in CIA, Louvain rats were immunized with type II collagen to induce arthritis and then administered an angiogenesis inhibitor, AGM-1470, in an attempt to either prevent arthritis or suppress established disease. Using clinical and radiographic criteria, AGM-1470 prevented CIA and significantly suppressed established disease without evidence of immunosuppression. Histologic sections from control ankle joints manifested pannus and neovascularization, which were absent in experimental animals. This is the first study to investigate this novel agent in an autoimmune disease, and additional evaluation of this promising compound in other diseases that are potentially angiogenesis dependent, such as rheumatoid arthritis, might be warranted.

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Collagen arthritis is induced in inbred rats with the injection of native type II collagen. The pathogenesis of this experimental autoimmune disease is T cell dependent. This study demonstrates that collagen-specific T cells, derived from pathogenic and nonpathogenic rat T cell lines, both recognize the same peptide epitope. The epitope, consisting of amino acids 58-73 of cyanogen bromide fragment 11 of type II collagen, was as effective as whole collagen in stimulating a panel of collagen-specific rat/mouse T cell hybridomas. This peptide may, therefore, constitute a dominant epitope for CD4+ rat T cells in their response to type II collagen. Administration of the peptide to either neonatal or adult rats prevented the subsequent induction of experimental arthritis with whole collagen, demonstrating that the in vivo response to this dominant epitope is, therefore, relevant in the pathogenesis of arthritis. Despite its ability to prevent collagen-induced arthritis, administration of this peptide in incomplete Freund's adjuvant intradermally did not induce disease.

Louvain (LOU) rats were administered either methotrexate (MTX; 0.3 mg/kg/week or 0.8 mg/kg/week intraperitoneally), cyclosporin A (CSA; 4 mg/kg/day or 10 mg/kg/day continuous infusion via osmotic pump), or a combination of both agents. The rats were immunized with native type I1 collagen (CII) to determine the effects of these agents on collagen-induced arthritis, an animal model of rheumatoid arthritis. A significant decrease in the incidence (P < 0.01) and severity of arthritis by clinical (P < 0.05) and radiographic assessments (P < 0.05) was found in recipients of combination therapy, compared with controls. Delayed-type hypersensitivity reactions to CII were measured on day 26, and production of IgG antibody to CII was measured on days 7,14, and 26. IgG antibody was evident by day 7, and titers were near-maximal by day 14. Both delayed-type hypersensitivity and antibodies to CII were reduced in animals that received the higher dosage of CSA. Liver, kidney, and spleen specimens obtained from rats treated with CSA and MTX demonstrated no histologic abnormalities on light microscopy, compared with controls. These studies indicate that CSA and MTX in combina-

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