{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:22:43Z","timestamp":1760242963521,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T00:00:00Z","timestamp":1423785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Staphylococcal enterotoxin B (SEB) and related exotoxins are important virulence factors produced by Staphylococcus aureus as they cause human diseases such as food poisoning and toxic shock. These toxins bind directly to cells of the immune system resulting in hyperactivation of both T lymphocytes and monocytes\/macrophages. The excessive release of proinflammatory cytokines from these cells mediates the toxic effects of SEB. This study examined the inhibitory activities of an anti-inflammatory drug, sulfasalazine, on SEB-stimulated human peripheral blood mononuclear cells (PBMC). Sulfasalazine dose-dependently inhibited tumor necrosis factor \u03b1, interleukin 1 (IL-1) \u03b2, IL-2, IL-6, interferon \u03b3 (IFN\u03b3), and various chemotactic cytokines from SEB-stimulated human PBMC. Sulfasalazine also potently blocked SEB-induced T cell proliferation and NF\u03baB activation. These results suggest that sulfasalazine might be useful in mitigating the toxic effects of SEB by blocking SEB-induced host inflammatory cascade and signaling pathways.<\/jats:p>","DOI":"10.3390\/toxins7020553","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T10:40:07Z","timestamp":1423824007000},"page":"553-559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sulfasalazine Attenuates Staphylococcal Enterotoxin B-Induced Immune Responses"],"prefix":"10.3390","volume":"7","author":[{"given":"Teresa","family":"Krakauer","sequence":"first","affiliation":[{"name":"Department of Immunology, Molecular Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0065-2776(08)60534-9","article-title":"Superantigens and their potential role in human disease","volume":"54","author":"Kotzin","year":"1993","journal-title":"Adv. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1615\/CritRevImmunol.v30.i2.40","article-title":"Staphylococcal superantigen super-domains in immune evasion","volume":"30","author":"Langley","year":"2010","journal-title":"Crit. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"DeVries, A.S., Lesher, L., Schlievert, P.M., Rogers, T., Villaume, L.G., Danila, R., and Lynfield, R. (2011). Staphylococcal toxic shock syndrome 2000\u20132006: Epidemiology, clinical features, and molecular characteristics. PLoS One, 6.","DOI":"10.1371\/journal.pone.0022997"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.4049\/jimmunol.140.8.2484","article-title":"Binding of staphylococcal enterotoxin A to accessory cells is a requirement for its ability to activate human T cells","volume":"140","author":"Carlsson","year":"1988","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8941","DOI":"10.1073\/pnas.86.22.8941","article-title":"Interaction of Staphylococcus aureus toxin \u201csuperantigens\u201d with human T cells","volume":"86","author":"Choi","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1084\/jem.167.3.752","article-title":"Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon","volume":"167","author":"Jupin","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/S0171-2985(11)80362-1","article-title":"Superantigen mediated shock: A cytokine release syndrome","volume":"189","author":"Miethke","year":"1993","journal-title":"Immunobiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.4049\/jimmunol.158.4.1862","article-title":"Induction of acute inflammatory lung injury by staphylococcal enterotoxin B","volume":"158","author":"Neumann","year":"1997","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1600-065X.2008.00681.x","article-title":"The bacterial superantigen and superantigen-like proteins","volume":"225","author":"Fraser","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S1473-3099(09)70066-0","article-title":"Gram-positive toxic shock syndromes","volume":"9","author":"Lappin","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Krakauer, T., Buckley, M., and Fisher, D. (2010). Proinflammatory mediators of toxic shock and their correlation to lethality. Mediators Inflamm.","DOI":"10.1155\/2010\/517594"},{"key":"ref_12","unstructured":"Paul, W. (1998). Fundamental Immunology, Lippincott-Raven. [4th ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1111\/j.1538-7836.2003.00498.x","article-title":"Superantigen from Staphylococcus aureus induce procoagulant activity and monocyte tissue factor expression in whole blood and mononuclear cells via IL-1\u03b2","volume":"1","author":"Mattsson","year":"2003","journal-title":"J. Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1086\/381979","article-title":"Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: Implications for therapy of toxic shock syndrome","volume":"38","author":"Darenberg","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.3390\/toxins5091629","article-title":"Update on staphylococcal superantigen-induced signaling pathways and therapeutic interventions","volume":"5","author":"Krakauer","year":"2013","journal-title":"Toxins"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2165\/00003495-199550010-00009","article-title":"Sulfasalazine. A review of its pharmacological properties and therapeutic efficacy in the treatment of rheumatoid arthritis","volume":"50","author":"Rains","year":"1995","journal-title":"Drugs."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2165\/00003495-198600321-00005","article-title":"Pharmacological and biochemical actions of sullphasalazine","volume":"32","author":"Hoult","year":"1986","journal-title":"Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.4049\/jimmunol.156.5.1937","article-title":"The anti-inflammatory mechanism of sulfasalazine is related to adenosine release at inflamed sites","volume":"156","author":"Gadangi","year":"1996","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev.immunol.021908.132641","article-title":"Regulation and function of NF\u03baB transcription factors in the immune system","volume":"27","author":"Vallabhapurapu","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1080\/08830180802317957","article-title":"Nuclear factor-\u03baB: Fine-tuning a central integrator of diverse biologic stimuli","volume":"27","author":"Krakauer","year":"2008","journal-title":"Int. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1210\/en.2004-0809","article-title":"Sulfasalazine and BAY 11\u20137082 interfere with the nuclear factor-\u03baB and I\u03baB kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro","volume":"146","author":"Lappas","year":"2005","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1056\/NEJM199704103361506","article-title":"Nuclear factor-\u03baB: A pivotal transcription factor in chronic inflammatory disease","volume":"336","author":"Barnes","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5604","DOI":"10.4049\/jimmunol.150.12.5604","article-title":"Microbial superantigens induce NF-kappa B in the human monocytic cell line THP-1","volume":"150","author":"Trede","year":"1993","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1128\/CDLI.8.2.449-453.2001","article-title":"Suppression of endotoxin- and staphylococcal exotoxin-induced cytokines and chemokines by a phospholipase C inhibitor in human peripheral blood mononuclear cells","volume":"8","author":"Krakauer","year":"2001","journal-title":"Clin. Diagn. Lab. Immunol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/2\/553\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:42:41Z","timestamp":1760215361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/2\/553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,13]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,2]]}},"alternative-id":["toxins7020553"],"URL":"https:\/\/doi.org\/10.3390\/toxins7020553","relation":{},"ISSN":["2072-6651"],"issn-type":[{"type":"electronic","value":"2072-6651"}],"subject":[],"published":{"date-parts":[[2015,2,13]]}}}