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Neutralization of staphylococcal exotoxins in vitro by human-origin intravenous immunoglobulin

  • Chie YanagisawaEmail author
  • Hideaki Hanaki
  • Taiji Natae
  • Keisuke Sunakawa
ORIGINAL ARTICLE

Abstract

Human-origin intravenous immunoglobulin (IVIG) collected from healthy individuals was tested for its neutralizing activity against the hemolysin, toxic shock syndrome toxin-1 (TSST-1), and enterotoxins, produced by laboratory strains of methicillin-resistant Staphylococcus aureus (MRSA). The hemolytic activity of the culture supernatant against sheep red blood cells was reduced from 100% to 5.5% relative hemolysis in the presence of 0.156 mg protein/ml of IVIG. The maximum dilution endpoint of the culture supernatant for TSST-1-mediated latex aggregation was 32-fold. This level of TSST-1 activity was reduced to eightfold dilution by 0.78 mg protein/ml of IVIG, and the latex aggregation activity of undiluted TSST-1 in the culture supernatant was inhibited by 1.56 mg protein/ml of IVIG. Similarly, the enterotoxin A-mediated latex aggregation titer appeared to be a 320-fold dilution. This toxin activity was reduced to an 80-fold dilution and below a tenfold dilution by 0.049 through 0.78 and 1.56 mg protein/ml, respectively, of IVIG. These results show that IVIG has powerful neutralizing activity against hemolysin, TSST-1, and enterotoxin A. Therefore, IVIG may be useful for passive immunization therapy in patients suffering from diseases caused by MRSA exotoxins.

Key words

Methicillin-resistant Staphylococcus aureus (MRSA) Exotoxin Intravenous immunoglobulin (IVIG) 

References

  1. 1.
    Knopf, HJ 1997Nosocomial infections caused by multiresistant pathogens. Clinical management exemplified by multiresistant Staphylococcus aureus Urologe A3624854PubMedCrossRefGoogle Scholar
  2. 2.
    Chambers, HF 2001The changing epidemiology of Staphylococcus aureus Emerg Infect Dis717882PubMedGoogle Scholar
  3. 3.
    Marchese, A, Schito, GC, Debbia, EA 2000Emergence of drug-resistant gram-positive pathogenic bacteria (in Italian)J Chemother12124PubMedGoogle Scholar
  4. 4.
    Dinges, MM, Orwin, PM, Schlievert, PM 2000Exotoxins of Staphylococcus aureus Clin Microbiol Rev131634PubMedCrossRefGoogle Scholar
  5. 5.
    Katayama, T, Mino, T, Inaoka, C, Fujiwara, F, Miyamichi, T, Nakayama, M 2005Coagulase typing, production of toxin, drug sensibility, Staphylococcus aureus (in Japanese)J Osaka Med-Center & Res Inst Mater-Child-Health21247Google Scholar
  6. 6.
    Schmitz, FJ, MacKenzie, CR, Geisel, R, Wagner, S, Idel, H, Verhoef, J,  et al. 1997Enterotoxin and toxic shock syndrome toxin-1 production of methicillin resistant and methicillin sensitive Staphylococcus aureus strainsEur J Epidemiol13699708PubMedCrossRefGoogle Scholar
  7. 7.
    Wiseman, GM 1975The hemolysins of Staphylococcus aureus Bacteriol Rev3931744PubMedGoogle Scholar
  8. 8.
    Piao, C, Karasawa, T, Totsuka, K, Uchiyama, T, Kikuchi, K 2005Prospective surveillance of community-onset and healthcare-associated methicillin-resistant Staphylococcus aureus isolated from a university-affiliated hospital in JapanMicrobiol Immunol4995970PubMedGoogle Scholar
  9. 9.
    Bernel, A, Proft, T, Fraser, JD, Posnett, DN 1999Superantigens in human diseaseJ Clin Immunol1914957CrossRefGoogle Scholar
  10. 10.
    Labrecque, NJ, Thibodeau, J, Sékaly, RP 1993Interactions between staphylococcal superantigens and MHC class II moleculesSemin Immunol52332PubMedCrossRefGoogle Scholar
  11. 11.
    Uchiyama, T, Yan, XJ, Imanishi, K, Yagi, J 1994Bacterial superantigens–mechanism of T cell activation by the superantigens and their role in the pathogenesis of infectious diseasesMicrobiol Immunol3824556PubMedGoogle Scholar
  12. 12.
    Hurley, JM, Shimonkevitz, R, Hanagan, A, Enney, K, Boen, E, Malmstrom, S,  et al. 1995Identification of class II major histocompatibility complex and T cell receptor binding sites in the superantigen toxic shock syndrome toxin 1J Exp Med181222935PubMedCrossRefGoogle Scholar
  13. 13.
    Nakae, T, Hirayama, F, Hashimoto, M 2002Neutralizing activity of human immunoglobulin preparation against toxic shock syndrome toxin-1 (in Japanese)Kansenshogaku Zasshi76195202PubMedGoogle Scholar
  14. 14.
    Aarestrup, F, Larsen, H, Eriksen, N, Elsberg, C, Jensen, N 1999Frequency of α- and β-hemolysin in Staphylococcus aureus of bovine and human originAPMIS10742530PubMedCrossRefGoogle Scholar
  15. 15.
    Mehrotra, M, Wang, G, Johnson, WM 2000Multiplex PCR for detection of genes for Staphylococcus aureus enterotoxins, exfoliative toxins, toxic shock syndrome toxin 1, and methicillin resistanceJ Clin Microbiol3810325PubMedGoogle Scholar
  16. 16.
    Kitamura, K, Mikami, Y 2002Analysis of the physicochemical and biochemical property of various intravenous immunoglobulin preparationsBiotherapy1646776Google Scholar
  17. 17.
    Rayner, C, Munckhof, WJ 2005Antibiotics currently used in the treatment of infections caused by Staphylococcus aureus Intern Med J35316CrossRefGoogle Scholar
  18. 18.
    Schlievert, PM 1993Role of superantigens in human diseaseJ Infect Dis1679971002PubMedGoogle Scholar
  19. 19.
    Panlilio, AL, Culver, DH, Gaynes, RP, Banerjee, S, Henderson, TS, Tolson, JS,  et al. 1992Methicillin-resistant Staphylococcus aureus in U.S. hospitals, 1975–1991Infect Control Hosp Epidemiol135826PubMedCrossRefGoogle Scholar
  20. 20.
    Todd, JK 2005Staphylococcal infectionsPediatr Rev2644450PubMedGoogle Scholar
  21. 21.
    Schaad, UB 1985Syndromes caused by staphylococcal toxins (in German)Schweiz Rundsch Med Prax2211759Google Scholar
  22. 22.
    Syuji, T, Yogesh, KA, Sharyn, MW 1993Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigensJ Clin Invest916027Google Scholar

Copyright information

© Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2007

Authors and Affiliations

  • Chie Yanagisawa
    • 1
    Email author
  • Hideaki Hanaki
    • 1
  • Taiji Natae
    • 1
  • Keisuke Sunakawa
    • 2
  1. 1.Kitasato Research Center for Anti-infection DrugsTokyoJapan
  2. 2.Graduate School of Infection Control Sciences, Kitasato Institute for Life SciencesKitasato UniversityTokyoJapan

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