Preparation of a superantigen-adsorbing device and its superantigen removal efficacies in vitro and in vivo

• Published in: International journal of infectious diseases 2003-03, Vol.7 (1), p.21-28
• Main Authors: Miwa, Keishi, Fukuyama, Mayumi, Ida, Nobuo, Igarashi, Hideo, Uchiyama, Takehiko
• Format: Article
• Language: English
• Subjects: Adsorption; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Blood Component Removal - instrumentation; Blood Component Removal - methods; Emergency and intensive care: infection, septic shock; Enterotoxins - chemistry; Enterotoxins - isolation & purification; Exotoxins - chemistry; Exotoxins - isolation & purification; Extracorporeal Circulation - instrumentation; Extracorporeal Circulation - methods; Female; Humans; Intensive care medicine; Male; Medical sciences; Polystyrenes - chemistry; Rabbits; Sepsis - blood; Sepsis - therapy; Staphylococcus - metabolism; Streptococcus - metabolism; Superantigens - chemistry; Superantigens - isolation & purification; Time Factors
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/S1201-9712(03)90038-5

Objective: A new superantigen-adsorbing device (SAAD) was developed, and its characteristics and efficacy in septic animals were evaluated. Methods: The SAAD was prepared by stepwise chemical modification of a polystyrene-based composite fiber reinforced with polypropylene. Adsorption affinities for several factors and the biological effect of superantigen (SAg) removal were measured in vitro. Also, superantigen-infused rabbits were treated with SAAD, and the efficacy was evaluated in vivo. Results: When the SAAD was evaluated for its ability to adsorb SAg in human plasma (1 ng/mL each), the adsorption rates were 74%,76% and 85% for staphylococcal enterotoxins A, B and C, respectively, and 80% and 72% for toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A, respectively. In addition, the SAAD showed some affinity towards other molecules, such as streptococcal pyrogenic exotoxin B, R2-microglobulin, and vancomycin. Residual activities in whole blood samples containing TSST 1 (1 ng/mL) after incubation with the SAAD were 125 pg/mL for tumor necrosis factor alpha (TNF-α) production, and 359 pg/mL for interleukin-8 (IL-8) production (the initial activities: 194 pg/mL for TNF-α production, and 1029 pg/mL for IL-8 production). When TSST-1/lipopolysaccharide (LPS)-infused rabbits were subjected to extracorporeal blood purification with a SAAD column, 50% of the animals survived for a 14-day period after the infusion. In contrast, all control animals died within 3 days after the infusion. Conclusion: These results indicate that the SAg-adsorbing device may be useful in treating SAg-related diseases.