Collagen‐induced arthritis in rats

Abstract

When rats were injected intradermally with an oil emulsion of native type I1 collagen, they developed an inflammatory polyarthritis. The incidence and severity of arthritis increased as the amount of collagen injected was increased. Rats 4% weeks old were the most susceptible to the development of arthritis, whereas weanling and older animals were relatively resistant. There was no difference in incidence between males and females. Mononuclear cells from peripheral blood, lymph nodes, and spleen were cultured with type I1 collagen and responded maximally to a collagen concentration of 25 pg/ml. The earliest detectable response was in peripheral blood mononuclear cell cultures obtained 6 to 8 days after immunization. The response of lymph node and spleen cells tended to lag behind that of peripheral blood cells at the earlier time intervals. Antibodies were detected in sera by hemagglutination at 8 days postimmunization. Quantitation of IgM and IgG antibodies by radioimmunoassay showed good correlation with hemagglutination titers and increased binding of collagen by both classes of antibody in arthritic as compared to nonarthritic animals. It is clear that the de- velopment of both humoral and cellular immunity to type I1 collagen is associated with the development of arthritis and may be important in the pathogenesis of this disease.We have previously reported that approximately 40% of rats injected intradermally with an oil emulsion of heterologous or homologous type I1 collagen develop an inflammatory polyarthritis after a latent period of 12 to 20 days. Other types of collagen, cartilage proteoglycans, and denatured type I1 collagen are ineffective in inducing arthritis when injected in an identical manner (1,2). If animals are studied at a time when disease is well developed (21-28 days), arthritic animals have a significantly greater immune response to type I1 collagen than similarly injected nonarthritic rats (3). However, the early sequence of events in development of the immune response and its relation to clinical disease have not been adequately investigated.The present studies were undertaken to d e h e additional factors that might influence the development of collagen-induced arthritis and to evaluate the immunologic response occurring in peripheral blood, lymph nodes, and spleen at regular intervals after injection of type I1 collagen. These studies demonstrate the important influence of the immunizing dose of collagen, route of injection, and the age of the rats on the incidence and severity of arthritis. The early appearance of antibody to type I1 collagen and the quantitation of both IgG and IgM responses reported here suggest that the role of antibody to type I1 collagen in the pathogenesis of arthritis may be more significant than heretofore recognized.

Histopathological Study of Arthritic Lesions Induced by Immunization with Type II Collagen in DBA/1J Mouse

“…In mice, CA has been reported mainly in DBA/1J strain. Development of CA is considered to be closely associated with humoral and cellular autoimmunity to type II collagen [13,14,18]. In the present study, the coincidence of elevation of serum anti-type II collagen IgG and development of polyarthritis was recognized in all animals of the immunized group.…”

Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II.

“…The arthritogenic T lymphocyte lines bore the WI 3/25 marker of helper/delayed hypersensitivity T cells. It is unlikely that recipient rats irradiated by 750 rad could have contributed the B lymphocytes needed for formation of possibly arthritogenic antibodies (16), which suggests that the line cells might induce arthritis by a delayed hypersensitivity reaction triggered by a cross-reactive self-antigen.…”

Novel synthetic retinoic acid inhibits rat collagen arthritis and differentially affects serum immunoglobulin subclass levels

“…CIA in rats is an animal model for rheumatoid arthritis, requiring T cells [16], anti-CII antibody [17] and complement system [18] for its induction and persistence. Recent clinical reports on the presence of anti-CII antibody particularly in early rheumatoid arthritis further warrant its importance for studying the pathogenesis of rheumatoid arthritis [19].…”