Earlier reports had described the presence, in supernates of streptococcal steady-state cultures, of a macromolecular toxin which causes infiltrative and necrotic lesions in the heart and liver of rabbits and changes in the serum level of certain enzymes and lipids. In the present study, following treatment of the culture supernate concentrates with trichloroacetic acid and ethanol, and dialysis, material with these biologic activities has been found, in the dialysate, and was not excluded by Sephadex G-15. The molecular weight of the toxin, by this criterion, is near that of vitamin B12.
Although numerous epidemiological and clinical studies have shown a definite relationship between a previous infection with strains of Group A streptococci and the appearance of sequelae (rheumatic fever, arthritis, nephritis), the mechanisms which lead to their development are still not fully understood. Since man is the only animal species which suffers from natural infections with Group A streptococci, and since it is agreed that viable streptococci cannot usually be isolated from the lesions characteristic of the chronic complications, Koch’s postulate can at best incriminate these micro-organisms only in the etiology of the acute infections but not in their subsequent complications. Despite many attempts to duplicate rheumatic fever, arthritis and acute glomerulonephritis in laboratory animals including higher apes, as a rule, the tissue lesions which developed in some of the animals bore little resemblance to the human lesions, and no true duplication of a disease syndrome similar to that seen in human beings has been reported. Two major theories have been proposed by various investigators to explain the nature of poststreptococcal complications. One theory proposes that the toxic effects of some streptococcal products (streptolysins O and S, erythrogenic toxin, proteinase, cell-wall mucopeptide-polysaccharide complex) are responsible for the initiation of the chronic lesions in the heart, joint and kidney characteristic of poststreptococcal diseases. The second theory suggests that the immunopathological phenomena (immune complex disease, cross-reactive immunity, delayed hypersensitivity) which develop in certain pa- tients who have become sensitized to one or more of the streptococcal products are responsible for the initiation of the disease in man. These two hypotheses are not, of course, mutually exclusive. Although no unified theory has been advanced which adequately explains the nature of the various post- streptococcal complications, a combination of both views may fit many, if not all, the features characteristic of these sequelae. Some theories on the pathogenesis of human poststreptococcal diseases and on the mechanisms of tissue injury induced by Group A streptococci have been recently reviewed (Taranta and Uhr, 1971; Ginsburg, 19720, b). The purpose of this paper is to describe some of the mechanisms by which Group A streptococci localize and persist in mammalian tissues and to relate the experimental models to the pathogenesis of poststreptococcal sequelae in man.
