Influence of lymphatic tissue on the development of adjuvant-induced polyarthritis in rats.

The experimental model of rheumatoid arthritis has not yet been established. Currently, two acceptable models of rheumatoid disease are being studied (Pearson, 1964), i.e. adjuvant-induced polyarthritis in rats and homologous disease (Ryzewska and Ryzewski, 1965; Ryzewski and Ryzewska, 1965). Polyarthritis appearing in rats after a subcutaneous injection of spleen cell suspension or homogenate with Freund's adjuvant was first described by Stoerk, Bielifiski, and Budzilovich (1954). These results were confirmed by Pearson (1956), who used for the immunization skeletal muscles with Freund's adjuvant or adjuvant alone. The development of adjuvant-induced polyarthritis in rats and the course of the disease have since been described in greater detail (Waksman, Pearson, and Sharp, 1960; Ward and Jones, 1962b; Pearson, 1963). It was found that a single intradermal injection of Freund's adjuvant (killed tubercle-either saprophytic bacilli or chemical fractions of it, mineral oil, and an emulsifying agent) was sufficient to produce polyarthritis. The paw is the most effective site of injection. A few hours after adjuvant administration a local inflammatory reaction develops at the injection site and persists during the whole latent period of the disease. The onset of the disease usually occurs on the 10th to the 16th day or later, being characterized by polyarthritis which often affects many of the peripheral joints but also some of the joints in the tail and at the base of the spine. The arthritis may be transitory or may become chronic. Histologically, there is an acute and subacute synovitis with proliferation of synovial lining cells, mononuclear infiltration of the articular cartilage and para-articular tissues, invasion of bone and articular cartilage by connective tissue pannus, and periosteal new bone formation. These destructive changes often cause fibrous or bony ankylosis (Pearson and Wood, 1962). Adjuvant polyarthritis is accompanied by inflammatory lesions of other tissues, including acute and chronic dermatitis, inflammation of serous membranes manifested by diarrhoea and urethritis, and inflammatory changes in the eye giving rise to conjunctivitis, keratitis, and iritis. In the lymph nodes draining the adjuvant injection site, in the lungs, and occasionally in the liver, the typical "post-adjuvant miliary granulomata" can easily be shown. They consist of an oil drop in the middle with histiocytes and lymphocytes at the circumference (Pearson, Waksman, and Sharp, 1961). Jones and Ward (1963) also observed purulent infiltrations in the spleen capsule, pleura, bronchi, and heart muscles. The pathogenesis of adjuvant-induced polyarthritis in rats has not so far been established. Three main mechanisms may be involved: