Further investigation of the biological properties of streptococcal cells and their components has produced a model of erosive synovitis in rats. A single intraperitoneal injection of an aqueous suspension of whole cell sonicate of group A streptococci into Sprague-Dawley rats induced an acute arthritis which evolved into a prolonged inflammatory process characterized by several complete or partial remissions, joint deformity, and ankylosis. The toxic moiety is a peptidoglycan-polysaccharide fragment of the cell wall which persists in tissue. Histologic features of the arthritis include an acute exudative phase followed by an erosive synovitis that leads to destruction of cartilage and subchondral bone and fibrous ankylosis of the joints. The arthropathic properties of whole cell sonicates of several species of streptococci are compared along with studies of the ability of heat-killed, whole cells of groups A, B, and C streptococci to induce arthritis in rats. Whole cells induce arthritis after a latent period of 57-120 days when group A cells are injected and 7-10 days when group B cells are tested.

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The covalently bound polymers of peptidoglycan and group-specific polysaccharide (PG-APS) were isolated from the cell walls of group A streptococci. Arthritis was induced in rats with a single intraperitoneal injection of an aqueous suspension of PG-APS fragments derived by sonication. The joint lesions induced with this polydisperse suspension followed a bimodal pattern consisting of an acute phase, which reached a peak 5 days after injection and then receded, followed by a chronic, remittent, erosive arthritis lasting several months. The relative severities of the acute and chronic phases could be manipulated by selection of the size of PG-APS fragments. The fragments of PG-APS obtained by sonic treatment were resolved on the basis of size into three major populations by sucrose gradient or differential centrifugation. Based upon light scattering and gel filtration, the average molecular weight of the largest family of fragments was estimated to be about 500 x 106, the intermediate fragments were 50 x 106 daltons, and the predominant size in the smallest population was 5.3 x 106 daltons. The larger fragments induced negligible acute inflammation, but chronic disease became apparent 5 to 9 weeks after injection. The smallest fragments induced the most severe acute inflammation, with relatively little late, chronic joint disease. The particles of intermediate size induced moderate acute inflammation and the most severe chronic, erosive joint lesions. A single injection of fragments of the isolated peptidoglycan moiety of the PG-APS induced only a moderate acute inflammation ofjoints, with no apparent capacity to maintain the injury and induce chronic disease.

The intraperitoneal injection of an aqueous suspension of cell wall fragments from group A streptococci induces a chronic intermittent arthritis in rats that is associated with the persistence of cell wall material in joint tissues. The radiographic techniques utilized to study this experimental model are described and the radiologic findings encountered during the natural history of the disease are presented. The progressive erosive synovitis of this model is similar to that seen in rheumatoid arthritis.

Joint inflammation initially induced by intraarticular injection of an aqueous suspension of peptidoglycan-polysaccharide (PG-PS) fragments isolated from Streptococcus pyogenes was reactivated by systemic injection of a normally subarthropathic dose of homologous or heterologous cell wall polymers, including muramyl dipeptide and lipopolysaccharide. Reactivation was not correlated with the severity of the initial inflammatory reaction. Results of studies utilizing lZ5I-labeled PG-PS fragments suggested that reactivation was associated with increased localization of PG-PS fragments in the joint following reinjection. These results indicate that the initial injury of the joint by S pyagenes PG-PS fragments increases the susceptibility of the joint to subsequent injury. Furthermore, once the inflammatory reaction is initiated, it can be perpetuated by a variety of ubiquitous cell wall polymers derived from normal flora as well as from pathogenic bacteria.Rats given either a systemic or an intraarticular (IA) injection of an aqueous suspension of peptidoglycan-polysaccharide (PG-PS) fragments isolated from the cell walls of Streptococcus pyogenes develop inflammatory reactions of the synovium and surrounding tissues (1,2). Although initially similar in