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The pathogenesis of rheumatoid arthritis might be more easily understood and the efficacy of therapeutic measures might be more accurately assessed if a convenient animal replica of this disease were available for laboratory study. Intraperitoneal injection of homogenates of inflamed synovium taken at operation from patients with rheumatoid arthritis produces inflammatory swelling and deformity in the tail and extremities of a proportion of injected mice from a complement (C5)-deficient inbred strain. Swelling of the paws leads to limping of the affected mice. The lesions are transmissible from generation to generation. The results support the theory of a transmissible agent in the inflamed synovium of rheumatoid arthritis patients.

Mice injected intravenously with Mycoplasma arthritidis developed a chronic arthritis which persisted through at least 269 days. Rats similarly treated developed an acute short-term infection. The mouse disease was characterized by periods of remission and exacerbation and was proliferative in nature, gradually spreading to adjacent joints. M. arthritidis strain 158 P10 was found to be less arthritogenic for mice than for rats, but further passage of this strain in mice substantially increased its virulence. Unlike rats, mice appeared to be susceptible to a "toxin" of M. arthritidis and they developed a necrotic spreading abscess after subcutaneous administration of the organisms. Histopathological studies revealed that mice varied greatly in the degree of joint inflammation, destruction, and repair. The disease was characterized by (i) an initial acute phase with infiltration of the articular and periarticular tissues with polymorphonuclear leukocytes and a mild hyperplasia of the synovial membrane; (ii) a mixed acute-chronic phase in which new areas of acute inflammation developed alongside areas of chronic lesions; (iii) a chronic phase followed which was characterized by massive synovial proliferation with mononuclear cell infiltration, irregularity in the articulating cartilage, pannus formation, and "punched out" defects in cortical bone near cartilagenous osseous junctures. The clinical course and histopathological characteristics of the chronic phase of mouse arthritis induced by M. arthritidis closely resembled those of rheumatoid arthritis of man.

Rats infected intravenously with Salmonella enteritidis develop a chronic destructive polyarthritis. The joint lesions resemble those of human rheumatoid arthritis in distribution and pathology. On the basis of histological and microbiological studies, involvement does not appear to be the result of intra-articular sepsis. Instead, the data favor the view that transient infection incites an immunological response that localizes in the joint and becomes destructive.