{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:01:20Z","timestamp":1791352880015,"version":"4.3.1"},"reference-count":42,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:p>Although circulatory shock related to lethal toxin (LeTx) may play a primary role in lethality due to Bacillus anthracis infection, its mechanisms are unclear. We investigated whether LeTx-induced shock is associated with inflammatory cytokine and nitric oxide (NO) release. Sprague-Dawley rats with central venous and arterial catheters received 24-h infusions of LeTx (lethal factor 100 \u03bcg\/kg; protective antigen 200 \u03bcg\/kg) that produced death beginning at 9 h and a 7-day mortality rate of 53%. By 9 h, mean arterial blood pressure, heart rate, pH, and base excess were decreased and lactate and hemoglobin levels were increased in LeTx nonsurvivors compared with LeTx survivors and controls (diluent only) ( P \u2264 0.05 for each comparing the 3 groups). Despite these changes, arterial oxygen and circulating leukocytes and platelets were not decreased and TNF-\u03b1, IL-1\u03b2, IL-6, and IL-10 levels were not increased comparing either LeTx nonsurvivors or survivors to controls. Nitrate\/nitrite levels and tissue histology also did not differ comparing LeTx animals and controls. In additional experiments, although 24-h infusions of LeTx and Esherichia coli LPS produced similar mortality rates (54 and 56%, respectively) and times to death (13.2 \u00b1 0.8 vs. 11.0 \u00b1 1.7 h, respectively) compared with controls, only LPS reduced circulating leukocytes, platelets, and IL-2 levels and increased TNF-\u03b1, IL-1\u03b1 and -1\u03b2, IL-6, IL-10, interferon-\u03b3, granulocyte macrophage-colony stimulating factor, RANTES, migratory inhibitory protein-1\u03b1, -2, and -3, and monocyte chemotactic protein-1, as well as nitrate\/nitrite levels (all P \u2264 0.05 for the effects of LPS). Thus, in contrast to LPS, excessive inflammatory cytokine and NO release does not appear to contribute to the circulatory shock and lethality occurring with LeTx in this rat model. Although therapies to modulate these host mediators may be applicable for shock caused by LPS or other bacterial toxins, they may not with LeTx.<\/jats:p>","DOI":"10.1152\/ajpregu.00593.2003","type":"journal-article","created":{"date-parts":[[2004,3,5]],"date-time":"2004-03-05T21:03:06Z","timestamp":1078520586000},"page":"R699-R709","source":"Crossref","is-referenced-by-count":95,"title":["Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats"],"prefix":"10.1152","volume":"286","author":[{"given":"Xizhong","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahtab","family":"Moayeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Haley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Fitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaly","family":"Correa-Araujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Banks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Leppla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Q.","family":"Eichacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.8.1038"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/116.3.377"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.20.2554"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/112.3.226"},{"key":"REF6","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200204-302OC"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.2.1175-1177.2001"},{"key":"REF8","doi-asserted-by":"crossref","unstructured":"Ezzell JW, Ivins BE, and Leppla SH.Immunoelectrophoretic analysis, toxicity, and kinetics of in vitro production of the protective antigen and lethal factor components ofBacillus anthracistoxin.Infect Immun45: 761-767, 1984.","DOI":"10.1128\/IAI.45.3.761-767.1984"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1038\/ng763"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.80.6.2066"},{"key":"REF11","doi-asserted-by":"crossref","unstructured":"Friedlander AM.Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process.J Biol Chem261: 7123-7126, 1986.","DOI":"10.1016\/S0021-9258(17)38364-3"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10198"},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200307000-00016"},{"key":"REF14","doi-asserted-by":"crossref","unstructured":"Klein F, Haines BW, Mahlandt BG, DeArmon IA, and Lincoln RE.Dual nature of resistance mechanisms as revealed by studies of anthrax septicemia.J Bacteriol85: 1032-1038, 1963.","DOI":"10.21236\/AD0289683"},{"key":"REF15","doi-asserted-by":"publisher","DOI":"10.1126\/science.138.3547.1331"},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1994.tb07306.x"},{"key":"REF17","unstructured":"Leppla SH.Anthrax toxin. In:Bacterial Protein Toxins, edited by Aktories KJ. New York: Springer, 2000, p. 445-472."},{"key":"REF18","doi-asserted-by":"crossref","unstructured":"Little SF, Leppla SH, and Cora E.Production and characterization of monoclonal antibodies to the protective antigen component ofBacillus anthracistoxin.Infect Immun56: 1807-1813, 1988.","DOI":"10.21236\/ADA216203"},{"key":"REF19","doi-asserted-by":"crossref","unstructured":"Little SF, Leppla SH, and Friedlander AM.Production and characterization of monoclonal antibodies against the lethal factor component ofBacillus anthracislethal toxin.Infect Immun58: 1606-1613, 1990.","DOI":"10.21236\/ADA216203"},{"key":"REF20","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.20.2549"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.7.858"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17991"},{"key":"REF23","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.55.1.647"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-114-28656"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.3.823"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1006\/prep.2000.1208"},{"key":"REF27","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01502-1"},{"key":"REF28","doi-asserted-by":"crossref","unstructured":"Pezard C, Berche P, and Mock M.Contribution of individual toxin components to virulence ofBacillus anthracis.Infect Immun59: 3472-3477, 1991.","DOI":"10.1128\/IAI.59.10.3472-3477.1991"},{"key":"REF29","unstructured":"Proceedings of the International Workshop on Anthrax.International Workshop on Anthrax, edited by Turnbal PCB. Winchester, UK: Salsbury Medical Society, 1990."},{"key":"REF30","unstructured":"Pugin J.Toll-like receptors. In:Evolving Concepts of Sepsis and Septic Shock, edited by Eichacker PQ and Pugin J. Norwell: Kluwer Academic, 2000, p. 27-44."},{"key":"REF31","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jim.7000239"},{"key":"REF32","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/118.1.104"},{"key":"REF33","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007606921569"},{"key":"REF34","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007546505528"},{"key":"REF35","doi-asserted-by":"publisher","DOI":"10.1038\/173869a0"},{"key":"REF36","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-198801000-00001"},{"key":"REF37","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401732"},{"key":"REF38","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/118.1.85"},{"key":"REF39","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.1999.00893.x"},{"key":"REF40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1036973100"},{"key":"REF41","doi-asserted-by":"publisher","DOI":"10.1080\/1071576021000033112"},{"key":"REF42","unstructured":"Yoshifumi T, Takeda T, Honda T, and Miwatani T.Comparison of bacterial cardiotoxins: thermostable direct hemolysin from vibrio parahaemolyticus, striptolysin 0, and hemolysin from listeria monocytogenes.Biken J21: 1-8, 1978."}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00593.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T01:14:29Z","timestamp":1623719669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00593.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1152\/ajpregu.00593.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00593.2003","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4]]}}}