Possible Role of Streptococcus pyogenes in Mucocutaneous Lymph Node Syndrome. XV. Potential Utility of Streptococcal Pyrogenic Exotoxin Toxoid for the Prophylaxis and Treatment of MCLS

Mice made tolerant to streptococcal pyrogenic exotoxin (SPE) by neonatal inoculation with SPE emulsified in incomplete Freund's adjuvant demonstrated early thrombocytopenia followed by thrombocytosis. This state is the perfect counterpart of patients with mucocutaneous lymph node syndrome (MCLS). We have hypothesized that by inducing tolerance to SPE, the biological activities of the toxin might play leading roles in the pathogenesis of MCLS. In the present investigations, the efficacy of SPE on the prophylaxis and treatment of diseases caused by Streptococcus pyogenes (including MCLS) were monitored using the murine model system accompanied with a platelet-counting technique. The mice, rendered tolerant due to neonatal SPE inoculation and followed by immunization with SPE toxoid about 1 month prior to the provocative injections with SPE, demonstrated an almost complete lack of response to the provocation, keeping platelet counts within the normal range of values (except for a marginally significant thrombocytosis 7 days postprovocation). Moreover, anti-SPE titers of the sera from the mice sacrificed on day 35, at which point the observation was terminated, were proved to be markedly elevated when compared with controls. These findings seem to suggest that immunization with the toxoid could overcome tolerance, resulting in the production of an antitoxin. In a second experiment that examined the effect of administration with rabbit antiserum raised against the toxoid, the antiserum-treated mice demonstrated a transitory thrombocytosis on 7 days postprovocation with SPE, followed by an abrupt decrease in the number of platelets from day 10 onward. Such a finding was in complete agreement with that observed in tolerant mice administered with antiserum specific for SPE, suggesting a strong neutralizing activity against SPE of the antitoxoid serum. A third experiment evaluated the effect of F(ab')2 fragments of the rabbit antiserum to the toxoid on platelet activity. The tolerant mice passively administered i.v. with the F(ab')2 fractions demonstrated a complete lack of responsiveness, except for a small thrombocytosis on days 7 and 10.