{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:06:47Z","timestamp":1785643607024,"version":"3.56.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"1-2","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Immunology and Immunopathology"],"published-print":{"date-parts":[[2012,11]]},"DOI":"10.1016\/j.vetimm.2012.09.002","type":"journal-article","created":{"date-parts":[[2012,9,7]],"date-time":"2012-09-07T01:00:49Z","timestamp":1346979649000},"page":"90-100","source":"Crossref","is-referenced-by-count":18,"title":["Effects of a \u201ctwo-hit\u201d model of organ damage on the systemic inflammatory response and development of laminitis in horses"],"prefix":"10.1016","volume":"150","author":[{"given":"Elizabeth M.","family":"Tadros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim M.","family":"Newkirk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Horohov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.vetimm.2012.09.002_bib0005","first-page":"45","article-title":"Pulmonary intravascular macrophages and endotoxin-induced pulmonary pathophysiology in horses","volume":"74","author":"Aharonson-Raz","year":"2010","journal-title":"Can. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0010","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.2042-3306.1996.tb03090.x","article-title":"Induction of early-phase endotoxin tolerance in horses","volume":"28","author":"Allen","year":"1996","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0015","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/j.2042-3306.1999.tb03175.x","article-title":"The role of prostanoids and nitric oxide in endotoxin-induced hyporesponsiveness of equine digital blood vessels","volume":"31","author":"Bailey","year":"1999","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0020","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.vetimm.2008.11.009","article-title":"Plasma concentrations of endotoxin and platelet activation in the developmental stage of oligofructose-induced laminitis","volume":"129","author":"Bailey","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0025","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.vetimm.2008.11.013","article-title":"Sepsis-From human organ failure to laminar failure","volume":"129","author":"Belknap","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0030","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2746\/042516407X155406","article-title":"Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness: innate vs. adaptive immune response","volume":"39","author":"Belknap","year":"2007","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0035","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.it.2009.07.009","article-title":"Endotoxin tolerance: new mechanisms, molecules and clinical significance","volume":"30","author":"Biswas","year":"2009","journal-title":"Trends Immunol."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0040","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/bja\/77.1.110","article-title":"Sepsis and cytokines: current status","volume":"77","author":"Blackwell","year":"1996","journal-title":"Br. J. Anaesth."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0045","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S1479-666X(03)80018-5","article-title":"Surgical sepsis: dysregulation of immune function and therapeutic implications","volume":"1","author":"Boontham","year":"2003","journal-title":"Surgeon"},{"key":"10.1016\/j.vetimm.2012.09.002_bib0050","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0039-6060(05)80345-9","article-title":"Postinjury neutrophil priming and activation: an early vulnerable window","volume":"118","author":"Botha","year":"1995","journal-title":"Surgery"},{"key":"10.1016\/j.vetimm.2012.09.002_bib0055","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/nrd1854","article-title":"Animal models of sepsis: setting the stage","volume":"4","author":"Buras","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0060","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1179\/096805106X102246","article-title":"Compartmentalization of the inflammatory response in sepsis and SIRS","volume":"12","author":"Cavaillon","year":"2006","journal-title":"J. Endotoxin Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0065","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0002-9440(10)62505-9","article-title":"Molecular signatures of sepsis: multiorgan gene expression profiles of systemic inflammation","volume":"159","author":"Chinnaiyan","year":"2001","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0070","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate\u2013phenol\u2013chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0075","doi-asserted-by":"crossref","first-page":"890","DOI":"10.2460\/javma.238.7.890","article-title":"Clinical and immunologic assessment of sepsis and the systemic inflammatory response syndrome in cats","volume":"238","author":"Declue","year":"2011","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0080","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.2460\/ajvr.1985.46.06.1287","article-title":"Alterations in coagulation and hemograms of horses given endotoxins for 24h via hepatic portal infusions","volume":"46","author":"Duncan","year":"1985","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0085","doi-asserted-by":"crossref","first-page":"2103S","DOI":"10.1093\/jn\/136.7.2103S","article-title":"Gastrointestinal derived factors are potential triggers for the development of acute equine laminitis","volume":"136","author":"Elliott","year":"2006","journal-title":"J. Nutr."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0090","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4049\/jimmunol.161.1.440","article-title":"Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil chemoattractant in the lung: role in pulmonary inflammation following lipopolysaccharide","volume":"161","author":"Fan","year":"1998","journal-title":"J. Immunol."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0095","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2460\/ajvr.1975.36.04.441","article-title":"Equine laminitis of alimentary origin: an experimental model","volume":"36","author":"Garner","year":"1975","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0100","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cveq.2010.06.001","article-title":"Current concepts on the pathophysiology of pasture-associated laminitis","volume":"26","author":"Geor","year":"2010","journal-title":"Vet. Clin. North Am. Equine Pract."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0105","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.2042-3306.1983.tb01826.x","article-title":"Relationship between condition score, physical measurements and body fat percentage in mares","volume":"15","author":"Henneke","year":"1983","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0110","doi-asserted-by":"crossref","first-page":"624","DOI":"10.2460\/ajvr.70.5.624","article-title":"Effects of low-dose oligofructose treatment administered via nasogastric intubation on induction of laminitis and associated alterations in glucose and insulin dynamics in horses","volume":"70","author":"Kalck","year":"2009","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0115","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1365-2249.2005.02853.x","article-title":"One-hit, two-hit \u2026 is there really any benefit?","volume":"141","author":"Lang","year":"2005","journal-title":"Clin. Exp. Immunol."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0120","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.2042-3306.2010.00122.x","article-title":"Laminar inflammatory gene expression in the carbohydrate overload model of equine laminitis","volume":"43","author":"Leise","year":"2011","journal-title":"Equine Vet. J."},{"issue":"Suppl 38","key":"10.1016\/j.vetimm.2012.09.002_bib0125","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.2042-3306.2010.00275.x","article-title":"Exercise-induced increases in inflammatory cytokines in muscle and blood of horses","volume":"42","author":"Liburt","year":"2010","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0130","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.vetimm.2012.09.002_bib0135","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.2460\/ajvr.68.11.1205","article-title":"Early laminar events involving endothelial activation in horses with black walnut-induced laminitis","volume":"68","author":"Loftus","year":"2007","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0140","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.2460\/ajvr.1992.53.08.1285","article-title":"Induction of the acute-phase cytokine, hepatocyte-stimulating factor\/interleukin 6, in the circulation of horses treated with endotoxin","volume":"53","author":"MacKay","year":"1992","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0145","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2460\/ajvr.1991.52.04.533","article-title":"Tumor necrosis factor activity in the circulation of horses given endotoxin","volume":"52","author":"MacKay","year":"1991","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0150","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1378\/chest.107.4.1062","article-title":"Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time","volume":"107","author":"Meduri","year":"1995","journal-title":"Chest"},{"key":"10.1016\/j.vetimm.2012.09.002_bib0155","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1189\/jlb.0704382","article-title":"Linking the \u201ctwo-hit\u201d response following injury to enhanced TLR4 reactivity","volume":"77","author":"Murphy","year":"2005","journal-title":"J. Leukocyte Biol."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0160","article-title":"Changes in the bacterial populations in the equine hindgut following the addition of inulin to the diet","volume":"16","author":"Newbold","year":"2009","journal-title":"Proc. Br. Soc. Anim. Sci."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0165","doi-asserted-by":"crossref","first-page":"717","DOI":"10.2746\/042516409X464780","article-title":"Effect of lipopolysaccharide infusion on gene expression of inflammatory cytokines in normal horses in vivo","volume":"41","author":"Nieto","year":"2009","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0170","doi-asserted-by":"crossref","first-page":"360","DOI":"10.2746\/042516407X177448","article-title":"Equine laminitis: ultrastructural lesions detected 24\u201330h after induction with oligofructose","volume":"39","author":"Nourian","year":"2007","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0175","doi-asserted-by":"crossref","first-page":"885","DOI":"10.2460\/javma.230.6.885","article-title":"Risk factors for development of acute laminitis in horses during hospitalization: 73 cases (1997\u20132004)","volume":"230","author":"Parsons","year":"2007","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0180","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.2042-3306.1996.tb01588.x","article-title":"Basement membrane pathology: a feature of acute equine laminitis","volume":"28","author":"Pollitt","year":"1996","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0185","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cveq.2010.01.006","article-title":"Carbohydrate alimentary overload laminitis","volume":"26","author":"Pollitt","year":"2010","journal-title":"Vet. Clin. North Am. Equine Pract."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0190","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1136\/emj.16.3.163","article-title":"Multiple organ failure. How valid is the \u201ctwo hit\u201d model?","volume":"16","author":"Saadia","year":"1999","journal-title":"J. Accid. Emerg. Med."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0195","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/00075198-200104000-00008","article-title":"The liver as an immune organ","volume":"7","author":"Sheth","year":"2001","journal-title":"Curr. Opin. Crit. Care"},{"key":"10.1016\/j.vetimm.2012.09.002_bib0200","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.2042-3306.1987.tb02571.x","article-title":"Plasma endotoxin levels in horses subjected to carbohydrate induced laminitis","volume":"19","author":"Sprouse","year":"1987","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0205","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/01.shk.0000148053.66645.2e","article-title":"The development of acute respiratory distress syndrome after gut ischemia\/reperfusion injury followed by fecal peritonitis in pigs: a clinically relevant model","volume":"23","author":"Steinberg","year":"2005","journal-title":"Shock"},{"key":"10.1016\/j.vetimm.2012.09.002_bib0210","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.vetimm.2008.11.001","article-title":"Indices of inflammation in the lung and liver in the early stages of the black walnut extract model of equine laminitis","volume":"129","author":"Stewart","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0260","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.2460\/ajvr.73.9.1394","article-title":"Effects of continuous or intermittent lipopolysaccharide administration for 48h on the systemic inflammatory response in horses","volume":"73","author":"Tadros","year":"2012","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0220","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.2460\/ajvr.2002.63.1629","article-title":"Short-term effect of therapeutic shoeing on severity of lameness in horses with chronic laminitis","volume":"63","author":"Taylor","year":"2002","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0225","doi-asserted-by":"crossref","first-page":"852","DOI":"10.2746\/042516409X479027","article-title":"Effects of endotoxaemia and carbohydrate overload on glucose and insulin dynamics and the development of laminitis in horses","volume":"41","author":"T\u00f3th","year":"2009","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0230","doi-asserted-by":"crossref","first-page":"82","DOI":"10.2460\/ajvr.69.1.82","article-title":"Effects of an intravenous endotoxin challenge on glucose and insulin dynamics in horses","volume":"69","author":"T\u00f3th","year":"2008","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0235","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2746\/042516406776866327","article-title":"Equine laminitis induced with oligofructose","volume":"38","author":"van Eps","year":"2006","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0240","doi-asserted-by":"crossref","first-page":"130","DOI":"10.2460\/ajvr.69.1.130","article-title":"Effects of systemic inflammation on insulin sensitivity in horses and inflammatory cytokine expression in adipose tissue","volume":"69","author":"Vick","year":"2008","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0245","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.2460\/ajvr.1997.58.12.1376","article-title":"Evaluation of platelet activation and platelet-neutrophil aggregates in ponies with alimentary laminitis","volume":"58","author":"Weiss","year":"1997","journal-title":"Am. J. Vet. Res."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0250","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2746\/0425164054529418","article-title":"Endotoxaemia: a review with implications for the horse","volume":"37","author":"Werners","year":"2005","journal-title":"Equine Vet. J."},{"key":"10.1016\/j.vetimm.2012.09.002_bib0255","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1439-0442.2004.00684.x","article-title":"Effect of acute sublethal endotoxaemia on in vitro digital vascular reactivity in horses","volume":"52","author":"Zerpa","year":"2005","journal-title":"J. Vet. Med. A: Physiol. Pathol. Clin. Med."}],"container-title":["Veterinary Immunology and Immunopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0165242712003182?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0165242712003182?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:04:18Z","timestamp":1744070658000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165242712003182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":51,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["S0165242712003182"],"URL":"https:\/\/doi.org\/10.1016\/j.vetimm.2012.09.002","relation":{},"ISSN":["0165-2427"],"issn-type":[{"value":"0165-2427","type":"print"}],"subject":[],"published":{"date-parts":[[2012,11]]}}}