title: Application of a rat model of streptococcal shock to evaluate on-line hemoperfusion and removal of circulating superantigens.
abstract: OBJECTIVE
  To evaluate the efficacy of on-line hemoperfusion for the removal of circulating superantigens in a rat model of streptococcal shock.
  
  
  METHODS
  In vitro and experimental animal studies.
  
  
  METHODS
  University research laboratories.
  
  
  METHODS
  Chemically modified polystyrene-based composite fiber reinforced with polypropylene was formulated in discs and used to evaluate the removal of superantigenic toxins from culture supernatants in vitro, and from blood in vivo.
  
  
  RESULTS
  Incubation of streptococcal supernatant with a single disc reduced the concentration of the superantigen streptococcal pyrogenic exotoxin A from 90.9 +/- 12.7 ng/mL with the control fiber to 32.5 +/- 3.6 ng/mL with active fiber (p <.001). The active discs also brought about a dose-dependent reduction in mitogenic activity that was highly significant (counts reduced from 82,133 +/- 2747 using three control discs to 26,307 +/- 3547 with three active discs [p <.001]). Beginning 6 hrs after infection, animals were hemoperfused for 3 hrs over columns containing control or active fiber. At the end of the treatment period, there was a significant decrease in the number of circulating bacteria in the active group (3.5 x 10(4) vs. 3.1 x 10(3) colony-forming units/mL, p<.05). However, bacterial counts subsequently increased and by 15 hrs and at all subsequent time points, the number of circulating bacteria was no different between the two groups. There was a highly significant and sustained difference in circulating streptococcal pyrogenic exotoxin A levels between the groups. Streptococcal pyrogenic exotoxin A levels at 9 hrs were 19.9 ng/mL in the controls vs. 2.1 ng/mL in the active group (p =.05). Animals perfused over active fibers had a highly significant survival advantage compared with control or nonperfused groups (p <.01).
  
  
  CONCLUSIONS
  Hemoperfusion and on-line removal of superantigens merits further study as a possible treatment strategy for streptococcal shock syndromes. The mechanism by which the fibers are operating requires further investigation.
authors.affiliation: Department of Infectious Diseases & Microbiology, Faculty of Medicine, Imperial College of Science Technology & Medicine, Hammersmith Hospital, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Fenwick
authors.forename: Calvin
authors.initials: C
authors.lastname: Ryan
authors.forename: Shiranee
authors.initials: S
authors.lastname: Sriskandan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000097:blood; D005098:Exotoxins; D005260:Female; D006439:Hemodynamics; D006464:Hemoperfusion / Q000379:methods*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000097:blood; D008565:Membrane Proteins / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000276:immunology / Q000628:therapy*; D018709:Statistics, Nonparametric; D013290:Streptococcal Infections / Q000276:immunology / Q000628:therapy*; D013297:Streptococcus pyogenes; D018089:Superantigens / Q000097:blood*
chemical_list: D001426:Bacterial Proteins; D005098:Exotoxins; D015850:Interleukin-6; D008565:Membrane Proteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens