Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Komisar, J. L.
Right arrow Articles by Tseng, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Komisar, J. L.
Right arrow Articles by Tseng, J.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CYCLOSPORIN A
*HYDROCORTISONE
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Cellular and Cytokine Responses in the Circulation and Tissue Reactions in the Lung of Rhesus Monkeys (Macaca mulatta) Pretreated with Cyclosporin A and Challenged with Staphylococcal Enterotoxin B

Jack L. Komisar

Department of Experimental Pathology, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, Jack.Komisar{at}na.amedd.Arm y.mil

Ching-Feng Weng

Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, R.O.C.

Adelekan Oyejide

Allergan, Inc, 2525 Dupont Drive, Irvine, CA 92612

Robert E. Hunt

Battelle Memorial Institute, 505 King Ave, Columbus, OH 43201

Crystal Briscoe

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground-EA, MD 21010

Jeenan Tseng

Department of Experimental Pathology, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500

Cyclosporin A (CsA), an inhibitor of T cell cytokine production, protects mice against staphylococca l enterotoxin B (SEB) intoxication. To determine whether CsA treatment would work in a species closer to humans, 4 rhesus monkeys were given 50 mg/kg CsA followed by an intratracheal challenge with approximately 6 LD50 of SEB. The CsA was not protective: one of the monkey s died and the other three had to be euthanized when they became moribund. All monkeys made IL-2, TNF, and IFN-{gamma} in response to SEB. In addition, there was about a 10-fold increase in ACTH levels 2 hr after SEB challenge. CsA significantly suppressed in vitro proliferation of lymphocytes from treated monkeys. Both CsA-treated monkeys and monkeys that had been challenged in a previous experiment with a lethal dose of SEB but had received no cyclosporin had pathologic changes in several organs. The most prominent changes were marked edema and leukocytic infiltration of the bronchial and bronchiolar mucosa. The CsA treatment appeared to reduce the intensity of lung inflammation, but this effect was not sufficient to protect the monkeys. The results suggest that CsA alone may not be an effective therapeutic agent for humans suffering from SEB intoxication or gram-positive septic shock.

Key Words: Cytokines • immunosuppression • neutrophils • shock • superantigens • T lymphocytes • toxin

References

  • Barton BE, Shortall J., Jackson JV (1996). Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model. Infect Immun 64: 714—718.[Abstract]
  • Bean AGD, Freiberg RA, Andrade S., Menon S., Zlotnik A. (1993). Interleukin 10 protects mice against staphylococca l enterotoxin B-induced lethal shock. Infect Immun 61: 4937—4939.[Abstract/Free Full Text]
  • Beisel WR (1972). Pathophysiology of staphylococcal enterotoxin, type B, (SEB) toxemia after intravenous administration to monkeys. Toxicon 10: 433—440.[Medline] [Order article via Infotrieve]
  • Belldegrun A., Webb DE, Austin HA, Steinberg SM, White DE, Linehan WM, Rosenberg SA (1987). Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer. Ann Intern Med 106: 817—822.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bergdoll MS (1970). Enterotoxins. In: Microbial Toxins, Vol. III. Bacterial Protein Toxins, Montie TC, Kadis S, Ajl SJ (eds). Academic Press, NY, pp 265—326.
  • Bergdoll MS (1983). Enterotoxins. In: Staphylococci and Staphylococcal Infections, Vol. 2, Easmon CSF, Adlam C (eds). Academic Press, New York, pp 559—598.
  • Bhatti AR, Micusan VV (1996). A mouse model for staphylococcal enterotoxins toxicity. Microbios 86: 247—253.[Web of Science][Medline] [Order article via Infotrieve]
  • Billiau A. (1996). Interferon-{gamma}: Biology and role in pathogenesis. Adv Immunol 62: 61—130.[Web of Science][Medline] [Order article via Infotrieve]
  • Blank C., Luz A., Bendigs S., Erdmann A., Wagner H., Heeg K. ( 1997). Superantigen and endotoxin synergize in the induction of lethal shock. Eur J Immunol 27: 825—833.[Web of Science][Medline] [Order article via Infotrieve]
  • Bohach GA, Fast DJ, Nelson RD, Schlievert PM (1990). Staphylococcal and streptococcal pyrogenic toxins involved in toxic shock syndrome and related illnesses. Crit Rev Microbiol 17: 251—272.[Web of Science][Medline] [Order article via Infotrieve]
  • Bolton C., Borel JF, Cuzner ML, Davison AN, Turner AM (1982). Immunosuppression by cyclosporin A of experimental allergic encephalomyelitis. J Neurologic Sci 56: 147—153.
  • Borel JF (1989). Pharmacology of cyclosporine (Sandimmune) IV. Pharmacological properties in vivo. Pharmacol Rev 41: 259— 371.
  • Bourrié B., Benoît J-M., Derocq J-M., Esclangon M., Thomas C., Le Fur G., Casellas P. (1996). A sigma ligand, SR31747A, potently modulates staphylococcal enterotoxin B-induced cytokine production in mice. Immunology 88: 389—393.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Chen JY-J, Qiao Y., Komisar JL, Baze WB, Hsu I-C., Tseng J. (1994). Increased susceptibility to staphylococcal enterotoxin B intoxication in mice primed with actinomycin D. Infect Immun 62: 4626 — 4631.[Abstract/Free Full Text]
  • Cohen SBA, Parry SL, Feldmann M., Foxwell B. (1997). Autocrine and paracrine regulation of human T cell IL-10 production. J Immunol 158: 5596—5602.[Abstract]
  • Derynck R., Choy L. ( 1998). Transforming growth factor-β and its receptors. In: The Cytokine Handbook, 3rd ed., Thomson AW (ed). Academic Press, San Diego, pp 593—636.
  • Di Padova FE (1989). Pharmacology of cyclosporine (Sandimmune) V. Pharmacological effects on immune function: In vitro studies. Pharmacol Rev 41: 373—405.[Web of Science]
  • Evans SW, Whicher JT (1993). The cytokines: physiological and pathophysiological aspects. Adv Clin Chem 30: 1—88.[Web of Science][Medline] [Order article via Infotrieve]
  • Florquin S., Aaldering L. (1997). Superantigens: A tool to gain new insight into cellular immunity. Res Immunol Inst Pasteur 148: 373— 386.
  • Florquin S., Amraoui Z., Abramowicz D., Goldman M. (1994). Systemic release and protective role of IL-10 in staphylococcal enterotoxin B-induced shock in mice. J Immunol 153: 2618—2623.[Abstract]
  • Florquin S., Amraoui Z., Dubois C., Decuyper J., Goldman M. (1994). The protective role of endogenously synthesized nitric oxide in staphylococcal enterotoxin B-induced shock in mice. J Exp Med 180: 1153— 1158.
  • Florquin S., Amraoui Z., Goldman M. (1995). T cells made deficient in interleukin-2 production by exposure to staphylococcal enterotoxin B in vivo are primed for interferon-{gamma} and interleukin-10 secretion. Eur J Immunol 25: 1148—1153.[Web of Science][Medline] [Order article via Infotrieve]
  • Florquin S., Goldman M. (1996). Immunoregulatory mechanisms of T-cell-dependent shock induced by a bacterial superantigen in mice. Infect Immun 64: 3443—3445.[Web of Science][Medline] [Order article via Infotrieve]
  • Garvey MB, Black JM (1972). The detection of fibrinogen/fibrin degradation products by means of a new antibody-coated latex particle. J Clin Pathol 25: 680—682.[Abstract/Free Full Text]
  • Gaynor ER, Vitek L., Sticklin L., Creekmore SP, Ferraro ME, Thomas JX, Fisher SG, Fisher RI (1988). The hemodynamic effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 109: 953—958.[Abstract/Free Full Text]
  • Gonzalo JA, González-García A., Martínez-A C., Kroemer G. (1993). Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo. J Exp Med 177: 1239—1246.[Abstract/Free Full Text]
  • Guide for the Care and Use of Laboratory Animals. Department of Health and Human Services, Public Health Service, NIH Publication 86-23, Revised 1985. US Government Printing Office, Washington, DC.
  • Hack CE, Aarden LA, Thijs LG (1997). Role of cytokines in sepsis. Adv Immunol 66: 101—195.[Web of Science][Medline] [Order article via Infotrieve]
  • Hack CE, Ogilvie AC, Eisele B., Eerenberg AJM, Wagstaff J., Thijs LG (1993). C1-inhibitor substitution therapy in septic shock and in the vascular leak syndrome induced by high doses of interleukin-2. Intensive Care Med 19: S19—S28.[CrossRef][Medline] [Order article via Infotrieve]
  • Haskó G., Virág L., Egnaczyk G., Salzman AL, Szabó C. (1998). The crucial role of IL-10 in the suppression of the immunological response in mice exposed to staphylococcal enterotoxin B. Eur J Immunol 28: 1417— 1425.
  • Heeg K., Miethke T., Wagner H. (1996). Superantigen-mediated lethal shock: The functional state of ligand-reactive T cells. Curr Top Microbiol Immunol 216: 83—100.[Web of Science][Medline] [Order article via Infotrieve]
  • Kotzin BL, Leung DYM, Kappler J., Marrack P. (1993). Superantigens and their potential role in human disease. Adv Immunol 54: 99—166.[Web of Science][Medline] [Order article via Infotrieve]
  • Krakauer T. (1995). Differential inhibitory effects of interleukin-10, interleukin-4, and dexamethasone on staphylococcal enterotoxin-induced cytokine production and T cell activation. J Leukocyte Biol 57: 450— 454.
  • Krakauer T., Pitt L., Hunt RE (1997). Detection of interleukin-6 and interleukin-2 in serum of rhesus monkeys exposed to a nonlethal dose of staphylococcal enterotoxin B. Mil Med 162: 612—615.[Web of Science][Medline] [Order article via Infotrieve]
  • Kusnecov AW, Liang R., Shurin G. (1999). T-lymphocyte activation increases hypothalamic and amygdaloid expression of CRH mRNA and emotional reactivity to novelty. J Neurosci 19: 4533—4543.[Abstract/Free Full Text]
  • Lang R., Wagner H., Heeg K. ( 1995). Differential effects of the immunosuppressive agents cyclosporine and leflunomide in vivo. Transplantation 59: 382—389.[Web of Science][Medline] [Order article via Infotrieve]
  • LeClaire RD, Kell W., Bavari S., Smith TJ, Hunt RE (1996). Protective effects of niacinamide in staphylococcal enterotoxin-B-induced toxicity. Toxicology 107: 69—81.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Lehmann V., Freudenberg MA, Galanos C. 1987. Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med 165: 657—663.[Abstract/Free Full Text]
  • Marrack P., Blackman M., Kushnir E., Kappler J. (1990). The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells. J Exp Med 171:455—464.[Abstract/Free Full Text]
  • Matthys P., Mitera T., Heremans H., Van Damme J., Billiau A. (1995). 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 63: 1158— 1164.
  • Mattix ME, Hunt RE, Wilhelmsen CL, Johnson AJ, Baze WB ( 1995). Aerosolized staphylococcal enterotoxin B-induced pulmonary lesions in rhesus monkeys (Macaca mulatta). Toxicol Pathol 23: 262— 268.[Medline] [Order article via Infotrieve]
  • Miethke T., Wahl C., Heeg K., Echtenacher B., Krammer PH, Wagner H. (1992). T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: Critical role of tumor necrosis factor. J Exp Med 175: 91—98.[Abstract/Free Full Text]
  • Mountz JD, Baker TJ, Borcherding DR, Bluethmann H., Zhou T., Edwards CK (1995). Increased susceptibility of fas mutant MRL-lpr/lpr mice to staphylococcal enterotoxin B-induced septic shock. J Immunol 155: 4829— 4837.
  • Muraille E., De Smedt T., Andris F., Pajak B., Armant M., Urbain J., Moser M., Leo O. (1997). Staphylococcal enterotoxin B induces an early and transient state of immunosuppression characterized by Vβ -unrestricted T cell unresponsivenes s and defective antigen-presenting cell functions. J Immunol 158: 2638—2647.[Abstract]
  • Nagaki M., Muto Y., Ohnishi H., Yasuda S., Sano K., Naito T., Maeda T., Yamada T., Moriwaki H. (1994). Hepatic injury and lethal shock in galactosaminesensitized mice induced by the superantigen staphylococcal enterotoxin B. Gastroenterology 106: 450—458.[Web of Science][Medline] [Order article via Infotrieve]
  • Pettit GW, Yamada T., Wing DA, Jahrling PB (1978). Enterotoxic shock in rhesus monkeys. The role of selected bloodborne factors. Circulation Res 43:398—405.[Free Full Text]
  • Physicians' Desk Reference. 54th ed. 2000. Montvale, NJ Medical Economics Co.
  • Roessler WG, Kautter DA (1962). Modification of the Henderson apparatus for studying air-borne infections. Evaluations using aerosols of Listeria monocytogenes. J Infect Dis 110: 17—22.[Web of Science][Medline] [Order article via Infotrieve]
  • Sarawar SR, Blackman MA, Doherty PC (1994). Superantigen shock in mice with an inapparent viral infection. J Infect Dis 170: 1189— 1194.
  • Schantz EJ, Roessler WG, Wagman J., Spero L., Dunnery DA, Bergdoll MS (1965). Purification of staphylococcal enterotoxin B. Biochemistry 4: 1011— 1016.
  • Shin G-T., Khanna A., Ding R., Sharma VK, Lagman M., Li B., Suthanthiran M. (1998). In vivo expression of transforming growth factor-β 1 in humans. Stimulation by cyclosporine. Transplantation 65: 313—318.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Silverman SJ, Espeseth DA, Schantz EJ (1969). Effect of formaldehyde on the immunochemical and biological activity of staphylococcal enterotoxin B. J Bacteriol 98: 437—442.[Abstract/Free Full Text]
  • Sugiyama H., McKissic EM, Bergdoll MS, Heller B. (1964). Enhancement of bacterial endotoxin lethality by staphylococcal enterotoxin. J Infect Dis 114: 111—118.[Web of Science][Medline] [Order article via Infotrieve]
  • Tseng J., Komisar JL, Chen JY-J, Hunt RE, Johnson AJ, Pitt L., Rivera J., Ruble DL, Trout R., Vega A. ( 1993). Immunity and responses of circulating leukocytes and lymphocytes in monkeys to aerosolized staphylococcal enterotoxin B. Infect Immun 61: 391—398.[Abstract/Free Full Text]
  • Ulrich RG, Sidell S., Taylor TJ, Wilhelmsen CL, Franz DR (1997). Staphylococcal enterotoxin B and related pyrogeni c toxins. In: Textbook of Military Medicine. Part I. Warfare, Weaponry, and the Casualty, Zajtchuk R (ed). Office of the Surgeon General, Department of the Army, Washington, DC, pp 621—630
  • Van Snick J. (1990). Interleukin-6: an overview. Annu Rev Immunol 8: 253— 278.
  • Wallach D., Holtmann H., Engelmann H., Nophar Y. (1988). Sensitization and desensitization to lethal effects of tumor necrosis factor and IL-1. J Immunol 140: 2994—2999.[Abstract]
  • Weng C-F. (1994). Interactions of the immune and neuroendocrine systems in the response to the superantigen staphylococcal enterotoxin B. Ph.D. dissertation, University of Maryland.
  • Weng C-F., Komisar JL, Hunt RE, Johnson AJ, Pitt ML, Ruble DL, Tseng J. (1997). Immediate responses of leukocytes, cytokines and glucocorticoid hormones in the blood circulation of monkeys following challenge with aerosolized staphylococca l enterotoxin B. Internat Immunol 9: 1825 — 1836.[Abstract/Free Full Text]
  • Whiteside TL (1994). Cytokine measurements and interpretation of cytokine assays in human disease. J Clin Immunol 14: 327— 339.
  • Yan Z., Yang DCH, Neill R., Jett M. ( 1999). Production of tumor necrosis factor alpha in human T lymphocytes by staphylococcal enterotoxin B correlates with toxin-induced proliferation and is regulated through protein kinase C. Infect Immun 67: 6611—6618.[Abstract/Free Full Text]

Toxicologic Pathology, Vol. 29, No. 3, 369-378 (2001)
DOI: 10.1080/019262301316905336
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
M. Waclavicek, N. Stich, I. Rappan, H. Bergmeister, and M. M. Eibl
Analysis of the early response to TSST-1 reveals V{beta}-unrestricted extravasation, compartmentalization of the response, and unresponsiveness but not anergy to TSST-1
J. Leukoc. Biol., January 1, 2009; 85(1): 44 - 54.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
V. Savransky, V. Rostapshov, D. Pinelis, Y. Polotsky, S. Korolev, J. Komisar, and K. Fegeding
Murine Lethal Toxic Shock Caused by Intranasal Administration of Staphylococcal Enterotoxin B
Toxicol Pathol, June 1, 2003; 31(4): 373 - 378.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Komisar, J. L.
Right arrow Articles by Tseng, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Komisar, J. L.
Right arrow Articles by Tseng, J.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CYCLOSPORIN A
*HYDROCORTISONE
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?