STREPTOCOCCAL PYROGENIC EXOTOXIN A RELEASE, DISTRIBUTION, AND ROLE INA MURINE MODEL OF FASCIITIS AND MULTIORGAN FAILURE DUE TO STREPTOCOCCUS-PYOGENES

The role of streptococcal pyrogenic exotoxin A (SPEA) was evaluated in a murine model of fasciitis and multiorgan failure due to a toxigenic strain of Streptococcus pyogenes. Increased serum levels of SPEA at 1 5 and 21 h were associated with a survival time of <24 h. Levels of SP EA correlated with interleukin-6 levels. Immunostaining showed SPEA lo calized to renal and hepatic cells. Neutralizing rabbit antibody to SP EA was administered to mice challenged with S. pyogenes, but no effect on survival was observed, Vaccination of mice with recombinant SPEA e nhanced mortality due to streptococcal infection, despite the developm ent of neutralizing immunity to the toxin prior to infection. Hence, S PEA is produced systemically during S. pyogenes soft-tissue infection, and increased levels are associated with reduced survival. In this mo del, however, SPEA did not appear to play a dominant role in pathogene sis; passive immunization against SPEA was not protective, and active immunization enhanced mortality.