Therapeutic down-modulators of staphylococcal superantigen-induced inflammation and toxic shock

Toxins

Volumn 2, Issue 8, 2010, Pages 1963-1983

  Krakauer, Teresa ^a  

^a UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES   (United States)

Author keywords

Inflammatory mediators; Murine models; Staphylococcal superantigens; Therapeutics; Toxic shock

Indexed keywords

1 (5 ISOQUINOLINESULFONYL) 2 METHYLPIPERAZINE; AUTACOID; BORTEZOMIB; CHEMOKINE; CYTOKINE; DACTINOMYCIN; DEXAMETHASONE; DOXYCYCLINE; GALACTOSAMINE; GENISTEIN; IMMUNOGLOBULIN; LIPOPOLYSACCHARIDE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; NICOTINAMIDE; PENTOXIFYLLINE; PIRFENIDONE; RAPAMYCIN; STAPHYLOCOCCUS ENTEROTOXIN B; SUPERANTIGEN; T LYMPHOCYTE RECEPTOR; TRICYCLO[4.3.0.1]DECAN 9 YL XANTHOGENATE;

ANTIGEN BINDING; ANTIGEN PRESENTING CELL; BLOOD CLOTTING; DISEASE MODEL; DRUG MECHANISM; FEVER; HOST CELL; HUMAN; HYPOTENSION; IMMUNE SYSTEM; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MACROPHAGE; MONOCYTE; NEPHROTOXICITY; NONHUMAN; RECEPTOR BINDING; REVIEW; SEPTIC SHOCK; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TISSUE INJURY; TRANSGENIC MOUSE; VOMITING;

ANIMALS; CYTOKINES; ENTEROTOXINS; HISTOCOMPATIBILITY ANTIGENS CLASS II; HUMANS; INFLAMMATION; RECEPTORS, ANTIGEN, T-CELL; SHOCK, SEPTIC; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS; SUPERANTIGENS;

MURINAE;

EID: 79952092597     PISSN: None     EISSN: 20726651     Source Type: Journal    
DOI: 10.3390/toxins2081963     Document Type: Review

References (129)

1. Chesney, P.J.; Davis, P.J.; Purdy, W.K.; Wand, P.J.; Chesney, R.W. Clinical manifestations of toxic shock syndrome. JAMA 1981, 246, 741-748.
2. Marrack, P.; Kappler, J. The staphylococcal enterotoxins and their relatives. Science 1990, 248, 705-709.
3. Kotzin, B.L.; Leung, D.Y.M.; Kappler, J.; Marrack, P. Superantigens and their potential role in human disease. Adv. Immunol. 1993, 54, 99-166.
4. Kotb, M. Bacterial pyrogenic exotoxins as superantigens. Clin. Microbiol. Rev. 1995, 8, 411-426.
5. Fraser, J.; Arcus, V.; Kong, P.; Baker, E.; Proft, T. Superantigens-powerful modifiers of the immune system. Mol. Med. Today 2000, 6, 125-132.
6. McCormick, J.K.; Yarwood, J.M.; Schlievert, P.M. Toxic shock syndrome and bacterial superantigens: an update. Ann. Rev. Microbiol. 2001, 55, 77-104.
7. Proft, T.; Fraser, J.D. Bacterial superantigens. Clin. Exp. Immunol. 2003, 133, 299-306.
8. Fraser, J.D.; Proft, T. The bacterial superantigen and superantigen-like proteins. Immunol. Rev. 2008, 225, 226-243.
9. Choi, Y.; Kotzin, B.; Hernon, L.; Callahan, J.; Marrack, P.; Kappler, J. Interaction of Staphylococcus aureus toxin superantigens with human T cells. Proc. Natl. Acad. Sci. USA 1989, 86, 8941-8945.
10. Jupin, C.; Anderson, S.; Damais, C.; Alouf, J.E.; Parant, M. Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon. J. Exp. Med. 1988, 167, 752-761.
11. Parsonnet, J. Mediators in the pathogenesis of toxic shock syndrome: overview. Rev. Infect. Dis. 1989, 11, S263-S269.
12. Fischer, H.; Dohlsten, M.; Andersson, U.; Hedlund, P.; Ericsson, P.; Hansson, J.; Sjogren, H.O. Production of TNF-α and TNF-β by staphylococcal enterotoxin A activated human T cells. J. Immunol. 1990, 144, 4663-4668.
13. Trede, N.S.; Geha, R.S.; Chatila, T. Transcriptional activation of IL-1 beta and tumor necrosis factor-alpha genes by MHC class II ligands. J. Immunol. 1991, 146, 2310-2315.
14. See, R.H.; Kum, W.W., Chang, A.H.; Goh, S.H.; Chow, A.W. Induction of tumor necrosis factor and interleukin-1 by purified staphylococcal toxic shock syndrome toxin 1 requires the presence of both monocytes and T lymphocytes. Infect. Immun. 1992, 60, 2612-2618.
15. Krakauer, T. Inhibition of toxic shock syndrome toxin-induced cytokine production and T cell activation by interleukin 10, interleukin 4, and dexamethasone. J. Infect. Dis. 1995, 172, 988-992.
16. Tessier, P.A.; Naccache, P.H.; Diener, K.R.; Gladue, R.P.; Neotem, K.S.; Clark-Lewis, I.; McColl, S.R. Induction of acute inflammation in vivo by staphylococcal superantigens. II. Critical role for chemokines, ICAM-1, and TNF-alpha. J. Immunol. 1998, 161, 1204-1211.
17. Krakauer, T. The induction of CC Chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline. J. Leukco. Biol. 1999, 66, 158-164.
18. Krakauer, T. Immune response to staphylococcal superantigens. Immunol. Res. 1999, 20, 163-173.
19. Mattsson, E.; Herwald, H.; Egsten, A. Superantigen from Staphylococcus aureus induce procoagulant activity and monocyte tissue factor expression in whole blood and mononuclear cells via IL-1β. J. Thromb. Haemost. 2003, 1, 2569-2575.
20. Krakauer, T.; Vilcek, J.; Oppenheim, J.J. Proinflammatory cytokines: TNF and IL-1 families, chemokines, TGFß and others. In Fundamental Immunology, 4th ed.; Paul, W., Ed.; Lippincott-Raven: Philadelphia, PA, USA, 1998; pp. 775-811.
21. Vial, T.; Descotes, J. Immune-mediated side-effects of cytokines in human. Toxicology 1995, 105, 31-57.
22. Papageorgiou, A.C.; Acharya, K.R. Microbial superantigens: from structure to function. Trends Microbiol. 2000, 8, 369-375.
23. Monday, S.R.; Bohach, G.A. Properties of Staphylococcus aureus enterotoxins and toxic shock syndrome toxin-1. In The Comprehensive Sourcebook of Bacterial Protein Toxins; Alouf, J.E., Freer, J.H., Eds.; Academic: London, UK, 1999; pp. 589-610.
24. Kappler, J.W.; Herman, A.; Clements, J.; Marrack, P. Mutations defining functional regions of the superantigen staphylococcal enterotoxin B. J. Exp. Med. 1992, 175, 387-396.
25. Holmberg, S.D.; Blake, P.A. Staphylococcal food poisoning in the United States. New facts and old misconceptions. JAMA 1984, 251, 487-489.
26. Abdelnour, A.T.; Bremell, T.; Tarkowski, A. TSST-1 contributes to the arthritogenecity of Staphylococcus aureus. J. Infect. Dis. 1994, 170, 94-99.
27. Schwab, J.H.; Brown, R.R.; Anderle, S.K.; Schlievert, P.M. Superantigen can reactivate bacterial cell wall-induced arthritis. J. Immunol. 1993, 150, 4151-4159.
28. Brocke, S.; Hausmann, S.; Steinmam, L.; Wucherpfennig, K.W. Microbial peptides and superantigens in the pathogenesis of autoimmune diseases of the central nervous system. Semin. Immunol. 1998, 10, 57-67.
29. Yarwood, J.M.; Leung, D.Y.; Schlievert, P.M. Evidence for the involvement of bacterial superantigens in psoriasis, atopic dermatitis, and Kawasaki syndrome. FEMS Microbiol. Lett. 2000, 192, 1-7.
30. Origuchi, T.; Eguchi, K.; Kawabe, Y.; Yamashita, I.; Mizokami, A.; Ida, H.; Nagataki, S. Increased levels of serum IgM antibody to staphylococcal enterotoxin B in patients with rheumatoid arthritis. Ann. Rheum. Dis. 1995, 54, 713-732.
31. Meissner, H.C.; Leung, D.Y.M. Superantigens, conventional antigens and the etiology of Kawasaki syndrome. Pediatr. Infect. Dis. J. 2000, 19, 91-94.
32. Meissner, H.C.; Leung, D.Y.M. Kawasaki Syndrome: Where Are the Answers? Pediatrics 2003, 112, 672-676.
33. Mollick, J.A.; Chintagumpala, M.; Cook, R.G.; Rich, R.R. Staphylococcal exotoxin activation of T cells. Role of exotoxin-MHC class II binding affinity and class II isotype. J. Immunol. 1991, 146, 463-468.
34. Herrmann, T.; Acolla, R.S.; MacDonald, H.R. Different staphylococcal enterotoxins bind preferentially to distinct MHC class II isotypes. Eur. J. Immunol. 1989, 19, 2171-2174.
35. Herman, A.; Croteau, G.; Sekaly, R.P.; Kappler, J.; Marrack, P. HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells. J. Exp. Med. 1990, 172, 709-712.
36. Chintagumpala, M.M.; Mollick, J.A.; Rich, R.R. Staphylococcal toxins bind to different sites on HLA-DR. J. Immunol. 1991, 147, 3876-3882.
37. Scholl, P.; Sekaly, R.; Diez, A.; Glimcher, L.; Geha, R. Binding of toxic shock syndrome toxin-1 to murine major histocompatibility complex class II molecules. Eur. J. Immunol. 1990, 20, 1911-1916.
38. Thibodeau, J.; Cloutier, I.; Lavoie, P.M.; Labrecque, N.; Mourad, W.; Jardetzky, T.; Sekaly, R.P. Subsets of HLA-DR1 molecules defined by SEB and TSST-1 binding. Science 1994, 266, 1874-1878.
39. Ulrich, R.G.; Bavari, B.; Olson, M.A. Staphylococcal enterotoxins A and B share a common structural motif for binding class II major histocompatibility complex molecules. Nat. Struct. Biol. 1995, 2, 554-560.
40. Hudson, K.R.; Tiedemann, R.E.; Urban, R.G.; Lowe, S.C.; Strominger, J.L.; Fraser, J.D. Staphylococcal enterotoxin A has two cooperative binding sites on major histocompatibility complex class II. J. Exp. Med. 1995, 182, 711-720.
41. Tiedemann, R.E; Urban, R.J.; Strominger, J.L.; Fraser, J.D. Isolation of HLA-DR1.(staphylococcal enterotoxins A)2 trimers in solution. Proc. Natl. Acad. Sci. USA 1995, 92, 12156-12159.
42. Pless, D.D.; Ruthel, G.; Reinke, E.K.; Ulrich, R.G.; Bavari, S. Persistence of zinc-binding bacterial superantigens at the surface of antigen-presenting cells contributes to the extreme potency of these superantigens as T-cell activators. Infect. Immun. 2005, 73, 5358-5366.
43. Linsley, P.S.; Ledbetter, J.A. The role of the CD28 receptor during T cell responses to antigen. Ann. Rev. Immunol. 1993, 11, 191-212.
44. Fraser, J.; Newton, M.; Weiss, A. CD28 and T-cell antigen receptor signal transduction coordinately regulates interleukin 2 gene expression in response to superantigen stimulation. J. Exp. Med. 1992, 175, 1131-1134.
45. Krakauer, T. Costimulatory receptors for the superantigen staphyloccoccal enterotoxin B on human vascular endothelial cells and T cells. J. Leukco. Biol. 1994, 56, 458-463.
46. Mehindate, K.; al-Daccak, R.; Damdoumi, F.; Mourad, W. Synergistic effect between CD40 and class II signals overcomes the requirement for class II dimerization in superantigen-induced cytokine gene expression. Eur. J. Immunol. 1996, 26, 2075-2080.
47. Saha, B.; Jaklic, B.; Harlan, D.M.; Gray, G.S.; June, C.H.; Abe, R. Toxic shock syndrome toxin-1 induced death is prevented by CTLA4Ig. J. Immunol. 1996, 157, 3869-3875.
48. Carlsson, R.; Fischer, H.; Sjogren, H.O. Binding of staphylococcal enterotoxin A to accessory cells is a requirement for its ability to activate human T cells. J. Immunol. 1998, 140, 2484-2488.
49. Tiedemann, R.E.; Fraser, J.D. Cross-linking of MHC class II molecules by staphylococcal enterotoxin A is essential for antigen-presenting cell and T cell activation. J. Immunol. 1996, 157, 3958-3966.
50. Anderson, M.R.; Tary-Lehmann, M. Staphylococcal enterotoxin-B-induced lethal shock in mice is T-cell-dependent, but disease susceptibility is defined by the non-T-cell compartment. Clin. Immunol. 2001, 98, 85-94.
51. Chatila, T.; Geha, R.S. Signal transduction by microbial superantigens via MHC class II molecules. Immunol. Rev. 1993, 131, 43-59.
52. Chatila, T.; Wood, N.; Parsonnet, J.; Geha, R.S. Toxic shock syndrome toxin-1 induces inositol phospholipid turnover, protein kinase C translocation, and calcium mobilization in human T cells. J. Immunol. 1988, 140, 1250-1255.
53. Scholl, P.R.; Trede, N.; Chatila, T.A.; Geha, R.S. Role of protein tyrosine phosphorylation in monokine induction by the staphylococcal superantigen toxic shock syndrome toxin-1. J. Immunol. 1992, 148, 2237-2241.
54. Krakauer, T. Small nonpeptide inhibitors of staphylococcal superantigen-induced cytokine production and toxic shock. In Superantigens: Molecular Basis for Their Role in Human Diseases; Kotb, M., Fraser, J.D., Eds.; ASM: Washington, DC, USA, 2007; pp. 229-224.
55. Hewitt, C.; Lamb, J.; Hayball, J.; Hill, M.; Owen, M.; O'Hehir, R. MHC Independent clonal T cell anergy by direct interaction of staphylococcal enterotoxin B with the T-cell antigen receptor. J. Exp. Med. 1992, 175, 1493-1499.
56. Scheuber, P.H.; Denzlinger, C.; Wilker, D.; Beck, G.; Kepper, D.; Hammer, D.K. Staphylococcal enterotoxin B as a nonimmunological mast cell stimulus in primates: the role of endogenous cysteinyl leukotrienes. Int. Arch. Allergy Appl. Immunol. 1987, 82, 289-291.
57. Mourad, W.; Mehindate, K.; Schall, T.; McColl, S. Engagement of MHC class II molecules by superantigen induces inflammatory cytokine gene expression in human rheumatoid fibroblast-like synoviocytes. J. Exp. Med. 1992, 175, 613-616.
58. Hamad, A.R.; Marrack, P.; Kappler, J.W. Transcytosis of staphylococcal superantigen toxins. J. Exp. Med. 1997, 185, 1447-1454.
59. Peterson, M.L.; Ault, K.; Kremer, M.J.; Klingelhutz, A.J.; Davis, C.C.; Squier, C.A.; Schlievert, P.M. The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1. Infect. Immun. 2005, 73, 2164-2174.
60. McKay, D.M. Bacterial superantigens: provocateurs of gut dysfunction and inflammation? Trends Immunol. 2001, 22, 497-501.
61. Krakauer, T. Stimulant-dependent modulation of cytokines and chemokines by airway epithelial cells: cross- talk between pulmonary epithelial and peripheral blood mononuclear cells. Clin. Diagn. Lab. Immunol. 2002, 9, 126-131.
62. Shupp, J.W.; Jett, M.; Pontzer, C.H. Identification of a transcytosis epitope on staphylococcal enterotoxins. Infect. Immun. 2002, 1029, 313-318.
63. Pinchuk, I.V.; Beswick, E.J.; Saada, J.I.; Suarez, G.; Winston, J.; Mifflin, R.C.; Di Mari, J.F.; Powell, D.W.; Reyes, V.E. Monocyte chemoattractant protein-1 production by intestinal myofibroblasts in response to staphylococcal enterotoxin A: relevance to staphylococcal enterotoxigenic disease. J. Immunol. 2007, 178, 8097-8106.
64. Takeuchi, O.; Akira, S. Pattern recognition receptors and inflammation. Cell 2010, 140, 805-820.
65. Vallabhapurapu, S.; Karin, M. Regulation and function of NF-κB transcription factors in the immune system. Annu. Rev. Immunol. 2009, 27, 693-733.
66. Krakauer, T. Molecular therapeutic targets in inflammation: cyclooxygenase and NF-κB. Curr. Drug Targets Inflamm. Allergy 2004, 3, 317-324.
67. Keystone, E.C.; Ware, C.F. Tumor necrosis factor and anti-tumor necrosis factor therapies. J. Rheumatol. 2010, 85, 27-39.
68. Dunn, G.P.; Koebel, C.M.; Schreiber, R.D. Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 2006, 6, 836-848.
69. Wang, X.; Lupardus, P.; LaPorte, S.L.; Garcia, K.C. Structural biology of shared cytokine receptors. Annu. Rev. Immunol. 2009, 27, 27-60.
70. Luster, A.D.; Alon, R.; von Andrian, U.H. Immune cell migration in inflammation: present and future therapeutic targets. Nat. Immunol. 2005, 6, 1182-1190.
71. Neumann, B.; Engelhardt, B.; Wagner, H.; Holzmann, B. Induction of acute inflammatory lung injury by staphylococcal enterotoxin B. J. Immunol. 1997, 158, 1862-1871.
72. Krakauer, T.; Buckley, M.; Huzella, L.M.; Alves, D. Critical timing, location and duration of glucocorticoid administration rescues mice from superantigen-induced shock and attenuates lung injury. Int. Immunopharmacol. 2009, 9, 1168-1174.
73. Ettinger, R.; Panka, D.J.; Wang, J.K.; Stanger, B.Z.; Ju, S.T.; Marshak-Rothstein, A. Fas ligand-mediated cytotoxicity is directly responsible for apoptosis of normal CD4+ T cells responding to a bacterial superantigen. J. Immunol. 1995, 154, 4302-4308.
74. Proft, T.; Sriskandan, S.; Yang, L.; Fraser, J.D. Superantigens and streptococcal toxic shock syndrome. Emerg. Infect. Dis. 2003, 9, 1211-1218.
75. Sriskandan, S.; Unnikrishnan, M.; Krausz, T.; Dewchand, H.; Van Noorden, S.; Cohen, J.; Altmann, D.M. Enhanced susceptibility to superantigen-associated streptococcal sepsis in human leukocyte antigen-DQ transgenic mice. J. Infect. Dis. 2001, 184, 166-173.
76. Krakauer, T.; Pitt, L.; Hunt, R.E. Detection of IL-6 and IL-2 in serum of rhesus monkeys exposed to a nonlethal dose of staphylococcal enterotoxin B. Mil. Med. 1997, 162, 612-615.
77. Mattix, M.E.; Hunt, R.E.; Wilhelmsen, C.L.; Johnson, A.J.; Baze, W.B. Aerosolized staphylococcal enterotoxin B-induced pulmonary lesions in rhesus monkeys (Macaca mulatta). Toxicol. Pathol. 1995, 23, 262-268.
78. Goettelfinger, P.; Lecerf, F.; Berrih-Aknin, S.; German-Fattal, M. Cytokine deviation induced by intrathymic injection of staphylococcal enterotoxin B (SEB). Eur. Cytokine Netw. 2001, 12, 487-500.
79. Huzella, L.M.; Buckley, M.J.; Alves, D.A.; Stiles, B.G.; Krakauer, T. Central roles for IL-2 and MCP-1 following intranasal exposure to SEB: A new mouse model. Vet. Res. Sci. 2009, 86, 241-247.
80. Hodoval, L.F.; Morris, E.L.; Crawley, G.J.; Beisel, W.R. Pathogenesis of lethal shock after intravenous staphylococcal enterotoxin B in monkeys. Appl. Microbiol. 1968, 16, 187-192.
81. Spiekermann, G.M.; Nagler-Anderson, C. Oral adminstration of the bacterial superantigen staphylococcal enterotoxin B induces activation and cytokine production by T cells in murine gut-associated lymphoid tissue. J. Immunol. 1998, 161, 5825-5831.
82. Alber, G.; Scheuber, P.H.; Reck, B.; Sailer-Kramer, B.; Hartmann, A.; Krammer, D.K. Role of substance P in immediate-type skin reactions induced by staphylococcal enterotoxin B in unsensitized monkeys. J. Allergy Clin. Immunol. 1998, 84, 880-885.
83. Hu, D.L.; Zhu, G.; Mori, F.; Omoe, K.; Okada, M.; Wakabayashi, K.; Kaneko, S.; Shinagawa, K.; Nakane, A. Staphylococcal enterotoxin induces emesis through increasing serotonin release in intestine and it is downregulated by cannabinoid receptor 1. Cell Microbiol. 2007, 9, 2267-2277.
84. Stiles, B.G.; Bavari, S.; Krakauer, T.; Ulrich, R.G. Toxicity of staphylococcal enterotoxins potentiated by lipopolysaccharide: major histocompatibility complex class II molecule dependency and cytokine release. Infect. Immun. 1993, 61, 5333-5338.
85. Sugiyama, H.; McKissic, E.M.; Bergdoll, M.S.; Heller, B. Enhancement of bacterial endotoxin lethality by staphylococcal enterotoxin. J. Infect. Dis. 1964, 4, 111-118.
86. Miethke, T.; Wahl, C.; Heeg, K.; Echtenacher, B.; Krammer, P.H.; Wagner, H. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J. Exp. Med. 1992, 175, 91-98.
87. Miethke, T.; Wahl, C.; Heeg, K.; Echtenacher, B.; Krammer, P.H.; Wagner, H. Superantigen mediated shock: a cytokine release syndrome. Immunobiology 1993, 189, 270-284.
88. Sarawar, S.R.; Blackman, B.A.; Doherty, P.C. Superantigen shock in mice with an inapparent viral infection. J. Infect. Dis. 1994, 170, 1189-1194.
89. Chen, J.Y.; Qiao, Y.; Komisar, J.L.; Baze, W.B.; Hsu, I.C.; Tseng, J. Increased susceptibility to staphylococcal enterotoxin B intoxication in mice primed with actinomycin D. Infect. Immun. 1994, 62, 4626-4631.
90. Zhang, W.J.; Sarawar, S.; Nguyen, P; Daly, K.; Rehig, J.E.; Doherty, P.C.; Woodland, D.L.; Blackman, M.A. Lethal synergism between influenza infection and staphylococcal enterotoxin B in mice. J. Immunol. 1996, 157, 5049-5060.
91. Blank, C.; Luz, A.; Bendigs, S.; Erdmann, A.; Wagner, H.; Heeg, K. Superantigen and endotoxin synergize in the induction of lethal shock. Eur. J. Immunol. 1997, 27, 825-833.
92. Khan, A.A.; Priya, S.; Saha, B. IL-2 regulates SEB induced toxic shock syndrome in BALB/c mice. PLoS One 2009, 4, e8473.
93. Matthys, P.; Mitera, T.; Heremans, H.; Van Damme, J.; Billiau, A. Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice. Infect. Immun. 1995, 63, 1158-1164.
94. LeClaire, R.D.; Kell, W.; Bavari, S.; Smith, T.; Hunt, R.E. Protective effects of niacinamide in staphylococcal enterotoxin B induced toxicity. Toxicology 1996, 107, 69-81.
95. Krakauer, T.; Stiles, B.G. Pentoxifylline inhibits staphylococcal superantigen induced toxic shock and cytokine release. Clin. Diagn. Lab. Immunol. 1999, 6, 594-598.
96. Hale, M.L.; Margolin, S.B.; Krakauer, T., Roy, C.J.; Stiles, B.G. Pirfenidone blocks in vitro and in vivo effects of staphylococcal enterotoxin B. Infect. Immun. 2002, 70, 2989-2994.
97. Krakauer, T.; Buckley, M. Dexamethasone attenuates staphylococcal enterotoxin B-induced hypothermic response and protects mice from superantigen-induced toxic shock. Antimicrob. Agents Chemother. 2006, 50, 391-395.
98. Krakauer, T.; Buckley, M.; Fisher, D. Proinflammatory mediators of toxic shock and their Correlation to lethality. Mediators Inflamm. 2010, doi:10.1155/2010/517594.
99. Bean, A.G.; Freiberg, R.A.; Andrade, S.; Menon, S.; Zlotnik, A. Interleukin 10 protects mice against staphylococcal enterotoxin B-induced lethal shock. Infect. Immun. 1993, 61, 4937-4939.
100. Florquin, S.; Amraoui, Z.; Abramowicz, D.; Goldman, M. Systemic release and protective role of IL-10 in staphylococcal enterotoxin B-induced shock in mice. J. Immunol. 1994, 153, 2618-2623.
101. Sundstedt, A.; Hoiden, L.; Rosendahl, A.; Kalland, T.; van Rooijen, N.; Dohlsten, M. Immunoregulatory role of IL-10 during superantigen-induced-hyporesponsiveness in vivo. J. Immunol. 1997, 158, 180-186.
102. Miller, C.; Ragheb, J.; Schwartz, R. Anergy and cytokine-mediated suppression as distinct superantigen-induced tolerance mechanisms in vivo. J. Exp. Med.1999, 190, 53-64.
103. McCormack, J.E.; Callahan, J.E.; Kappler, J.; Marrack, P. Profound deletion of mature T cells in vivo by chronic exposure to endogenous superantigen. J. Immunol. 1993, 150, 3785-3792.
104. DaSilva, L.; Welcher, B.; Ulrich, R.; Aman, J.; David, C.S.; Bavari, S. Humanlike immune response of human leukocyte antigen-DR3 transgenic mice to staphylocococal enterotoxins: a novel model for superantigen vaccines. J. Infect. Dis. 2002, 185, 1754-1760.
105. Rajagopalan, G.; Sen, M.M.; David, C.S. In vitro and in vivo evaluation of staphylococcal superantigen peptide antagonists. Infect. Immun. 2004, 72, 6733-6737.
106. Roy, C.J.; Warfield, K.L.; Welcher, B.C.; Gonzales, R.F.; Larsen, T.; Hanson, J.; David, C.S.; Krakauer, T.; Bavari, S. Human leukocyte antigen-DQ8 transgenic mice: a model to examine the toxicity of aerosolized staphylococcal enterotoxin B. Infect. Immun. 2005, 73, 2452-2460.
107. Yeung, R.S.; Penninger, J.M.; Kundig, J.; Khoo, W.; Ohashi, P.S.; Kroemer, G.; Mak, T.W. Human CD4 and human major histocompatibility complex class II (DQ6) transgenic mice: supersensitivity to superantigen-induced septic shock. Eur. J. Immun. 1996, 26, 1074-1082.
108. Savransky, V.; Rostaphshov, V.; Pinelis, D.; Polotsky, Y.; Korolev, S.; Komisar, J.; Fegeding, K. Murine lethal toxic shock caused by intranasal administration of staphylococcal enterotoxin B. Toxicol. Pathol. 2003, 31, 373-378.
109. Stebbings, R.; Findlay, L.; Edwards, C.; Eastwood, D.; Bird, C.; North, D.; Mistry, Y.; Dilger, P.; Liefooghe, E.; Cludts, I.; et al. ''Cytokine Storm in the Phase I Trial of Monoclonal Antibody TGN1412: Better Understanding the Causes to Improve PreClinical Testing of Immunotherapeutics. J. Immunol. 2007, 179, 3325-3331.
110. Darenberg, J.; Soderquist, B.; Normark, B.H.; Norrby-Teglund, A. Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome. Clin. Infect. Dis. 2004, 38, 836-842
111. Bavari, S.; Ulrich, R.G.; LeClaire, R.D. Cross-reactive antibodies prevent the lethal effects of Staphylococcus aureus superantigens. J. Infect. Dis. 1999, 180, 1365-1369.
112. Bavari, S.; Dyas, B.; Ulrich, R.G. Superantigen vaccines: a comparative study of genetically attenuated receptor-binding mutants of staphylococcal enterotoxin A. J. Infect. Dis. 1996, 174, 338-345.
113. Arad, G.; Levy, R.; Hillman, D.; Kaempfer, R. Superantigen antagonist protects against lethal shock and defines a new domain for T-cell activation. Nat. Med. 2000, 6, 414-421.
114. Visvanathan, K.; Charles, A.; Bannan, J.; Pugach, P.; Kashfi, K.; Zabriskie, J.B. Inhibition of bacterial superantigens by peptides and antibodies. Infect. Immun. 2001, 69, 875-884.
115. Wang, S.; Li, Y.; Xiong, H.; Cao, J. A broad-spectrum inhibitory peptide against staphylococcal enterotoxin superantigen SEA, SEB and SEC. Immunol. Lett. 2008, 121, 167-172.
116. Geller-Hong, E.; Möllhoff, M.; Shiflett, P.R.; Gupta, G. Design of chimeric receptor mimics with different TcRVβ isoforms: type-specific inhibition of superantigen pathogenesis. J. Biol. Chem. 2004, 279, 5676-5684.
117. Rasooly, R.; Do, P.M.; Friedman, M. Inhibition of biological activity of staphylococcal enterotoxin A (SEA) by apple juice and apple polyphenols. J. Agric. Food Chem. 2010, 58, 5421-5426.
118. Liu, D.; Liu, X.Y.; Robinson, D.; Burnett, C.; Jackson, C.; Seele, L.; Veach, R.A.; Downs, S.; Collins, R.D.; Ballard, R.W.; Hawiger, J. Suppression of staphylococcal enterotoxin B-induced toxicity by a nuclear import inhibitor. J. Biol. Chem. 2004, 279, 19239-19246.
119. Liu, D.; Zienkiewicz, J.; DiGiandomenico, A.; Hawiger, J. Suppression of acute lung inflammation by intracellular peptide delivery of a nuclear import inhibitor. Mol. Ther. 2009, 17, 796-802.
120. Tilahun, A.Y.; Theuer, J.E.; Patel, R.; David, C.S.; Rajagopalan, G. Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation. Mol. Ther. 2010, 18, 1143-1154.
121. Krakauer, T. A sensitive ELISA for measuring the adhesion of leukocytic cells to human endothelial cells. J. Immunol. Meth. 1994, 177, 207-213.
122. See, R.H.; Chow, A.W. Staphylococcal toxic shock syndrome toxin 1-induced tumor necrosis factor alpha and interleukin-1ß secretion by human peripheral blood monocytes and T lymphocytes is differentially suppressed by protein kinase inhibitors. Infect. Immun. 1992, 60, 3456-3459.
123. Krakauer, T. Suppression of endotoxin- and staphylococcal exotoxin-induced cytokines and chemokines by a phospholipase C inhibitor in human peripheral blood mononuclear cells. Clin. Diagn. Lab. Immunol. 2001, 8, 449-453.
124. Tschaikowsky, K.J.; Schmidt, J.; Meisner, M. Modulation of mouse endotoxin shock by inhibition of phosphatidylcholine-specific phospholipase C. J. Pharmacol. Exp. Therap. 1999, 285, 800-804.
125. Krakauer, T.; Buckley, M.; Issaq, H.J.; Fox, S.D. Rapamycin protects mice from staphylococcal enterotoxin B- induced toxic shock and blocks cytokine release in vitro and in vivo. Antimicrob. Agents Chemother. 2010, 54, 1125-1131.
126. Flechner, S.M. Sirolimus in kidney transplantation indications and practical guidelines: de novo sirolimus-based therapy without calcineurin inhibitors. Transplantation 2009, 97, S1-S6.
127. Krakauer, T. Caspase inhibitors attenuate superantigen-induced inflammatory cytokines, chemokines and T-cell proliferation. Clin. Diagn. Lab. Immunol. 2004, 11, 621-624.
128. Krakauer, T.; Buckley, M. Doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced cytokines and chemokines. Antimicrob. Agents Chemother. 2003, 47, 3630-3633.
129. Jo, D.; Liu, D.; Yao, S.; Collins, R.D.; Hawiger, J. Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis. Nat. Med. 2005, 11, 892-898.