{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:35:50Z","timestamp":1777019750478,"version":"3.51.4"},"reference-count":53,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministerstwo Edukacji i Nauki","doi-asserted-by":"publisher","award":["2 P05F 032 30"],"award-info":[{"award-number":["2 P05F 032 30"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2009,4]]},"DOI":"10.1016\/j.intimp.2009.01.013","type":"journal-article","created":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T04:43:25Z","timestamp":1233204205000},"page":"478-490","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"title":["Pretreatment with R(+)-verapamil significantly reduces mortality and cytokine expression in murine model of septic shock"],"prefix":"10.1016","volume":"9","author":[{"given":"El\u017cbieta","family":"Wyska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.intimp.2009.01.013_bib1","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/S0140-6736(98)01134-9","article-title":"Septic shock","volume":"351","author":"Astiz","year":"1998","journal-title":"Lancet"},{"key":"10.1016\/j.intimp.2009.01.013_bib2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/089419301750420232","article-title":"Animal models of sepsis","volume":"14","author":"Freize","year":"2001","journal-title":"J Invest Surg"},{"key":"10.1016\/j.intimp.2009.01.013_bib3","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1097\/00005344-198811000-00007","article-title":"Electrophysiologic effects of dextro- and levo-verapamil on sinus node and AV node function in humans","volume":"12","author":"Echizen","year":"1988","journal-title":"J Cardiovasc Pharmacol"},{"key":"10.1016\/j.intimp.2009.01.013_bib4","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/BF00315139","article-title":"Effects of verapamil enantiomers and major metabolites on the cytotoxicity of vincristine and daunomycin in human cell lines","volume":"40","author":"H\u00e4ubermann","year":"1991","journal-title":"Eur J Clin Pharmacol"},{"key":"10.1016\/j.intimp.2009.01.013_bib5","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2165\/00003088-200746060-00001","article-title":"Expression of adenosine triphosphate-binding cassette (ABC) drug transporters in peripheral blood cells. Relevance for physiology and pharmacotherapy","volume":"46","author":"K\u00f6ck","year":"2007","journal-title":"Clin Pharmacokinet"},{"key":"10.1016\/j.intimp.2009.01.013_bib6","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1182\/blood.V88.5.1747.1747","article-title":"Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-\u03b3 in normal human T lymphocytes","volume":"88","author":"Drach","year":"1996","journal-title":"Blood"},{"key":"10.1016\/j.intimp.2009.01.013_bib7","first-page":"1258","article-title":"Monoclonal antibodies against P-glycoprotein, an MDR1 gene product, inhibit interleukin-2 release from PHA-activated lymphocytes","volume":"24","author":"Raghu","year":"1996","journal-title":"Exp Hematol"},{"key":"10.1016\/j.intimp.2009.01.013_bib8","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1211\/jpp.57.11.0007","article-title":"Involvement of P-glycoprotein in the release of cytokines from peripheral blood mononuclear cells treated with methotrexate and dexamethasone","volume":"57","author":"Pawlik","year":"2005","journal-title":"J Pharm Pharmacol"},{"key":"10.1016\/j.intimp.2009.01.013_bib9","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.4049\/jimmunol.163.5.2621","article-title":"mdr1a-encoded P-glycoprotein is not required for peripheral T cell proliferation, cytokine release, or cytotoxic effector function in mice","volume":"163","author":"Eisenbraun","year":"1999","journal-title":"J Immunol"},{"key":"10.1016\/j.intimp.2009.01.013_bib10","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/biot.200600236","article-title":"Enantioselective reduction of pentoxifylline to lisofylline using whole-cell Lactobacillus kefiri biotransformation","volume":"4","author":"P\u0119kala","year":"2007","journal-title":"J Biotech"},{"key":"10.1016\/j.intimp.2009.01.013_bib11","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1006\/meth.2001.1261","article-title":"An overview of real-time quantitative PCR: applications to quantify cytokine gene expression","volume":"25","author":"Giulietti","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.intimp.2009.01.013_bib12","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.intimp.2009.01.013_bib13","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative expressive software tool (REST\u00a9) for group-wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.intimp.2009.01.013_bib14","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1097\/00007890-199210000-00023","article-title":"Evidence that the antiproliferative effect of verapamil on afferent and efferent immune responses is independent of calcium channel inhibition","volume":"54","author":"Weir","year":"1992","journal-title":"Transplantation"},{"key":"10.1016\/j.intimp.2009.01.013_bib15","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s00011-005-0060-y","article-title":"Verapamil modulates LPS-induced cytokine production via inhibition of NF-kappa B activation in the liver","volume":"55","author":"Li","year":"2006","journal-title":"Inflamm Res"},{"key":"10.1016\/j.intimp.2009.01.013_bib16","first-page":"434","article-title":"Slow channel calcium inhibition blocks proinflammatory gene signaling and reduces macrophage responsiveness","volume":"52","author":"Cuschieri","year":"2002","journal-title":"J Trauma"},{"key":"10.1016\/j.intimp.2009.01.013_bib17","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/00003246-199302000-00009","article-title":"Human sepsis increases lymphocyte intracellular calcium","volume":"21","author":"Zaloga","year":"1993","journal-title":"Crit Care Med"},{"key":"10.1016\/j.intimp.2009.01.013_bib18","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1073\/pnas.90.9.3933","article-title":"Increased intracellular Ca2+: a critical link in the pathophysiology of sepsis?","volume":"90","author":"Song","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.intimp.2009.01.013_bib19","doi-asserted-by":"crossref","first-page":"G920","DOI":"10.1152\/ajpgi.1996.271.5.G920","article-title":"Endocytosis and Ca2+ are required for endotoxin-stimulated TNF-alpha release by rat Kupffer cells","volume":"271","author":"Lichtman","year":"1996","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.intimp.2009.01.013_bib20","first-page":"337","article-title":"Calcium antagonists decrease plasma and tissue concentrations of tumor necrosis factor-\u03b1, interleukin-1\u03b2, and interleukin-1\u03b1 in a mouse model of endotoxin","volume":"3","author":"Hotchkiss","year":"1995","journal-title":"Shock"},{"key":"10.1016\/j.intimp.2009.01.013_bib21","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/sj.gene.6363693","article-title":"P-glycoprotein (encoded by multidrug resistance genes) is not required for interleukin-2 secretion in mice and humans","volume":"1","author":"Gollapudi","year":"2000","journal-title":"Genes Immun"},{"key":"10.1016\/j.intimp.2009.01.013_bib22","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1128\/AAC.44.11.3169-3173.2000","article-title":"Protection against lipopolysaccharide-induced death by fluoroquinolones","volume":"44","author":"Khan","year":"2000","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.intimp.2009.01.013_bib23","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1172\/JCI119475","article-title":"MCP-1 protects mice in lethal endotoxemia","volume":"99","author":"Zisman","year":"1997","journal-title":"J Clin Invest"},{"key":"10.1016\/j.intimp.2009.01.013_bib24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1006\/cyto.2002.1948","article-title":"Cytokine expression in three mouse models of experimental hepatitis","volume":"19","author":"Sass","year":"2002","journal-title":"Cytokine"},{"key":"10.1016\/j.intimp.2009.01.013_bib25","doi-asserted-by":"crossref","DOI":"10.1007\/BF01991143","article-title":"Production of TNF alpha by LPS-stimulated murine, rat, and human blood and its pharmacological modulation","volume":"38","author":"Foster","year":"1993","journal-title":"Agents Actions"},{"key":"10.1016\/j.intimp.2009.01.013_bib26","first-page":"30","article-title":"Differential effect of pentoxifylline on the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by monocytes and T cells","volume":"76","author":"Schandene","year":"1992","journal-title":"Immunology"},{"key":"10.1016\/j.intimp.2009.01.013_bib27","first-page":"8","article-title":"Pharmacological modulation of TNF alpha production in macrophages","volume":"37","author":"Lin","year":"2004","journal-title":"J Microbiol Immunol Infect"},{"key":"10.1016\/j.intimp.2009.01.013_bib28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1084\/jem.172.1.391","article-title":"Dexamethasone and pentoxifylline inhibit endotoxin-induced catechin\/tumor necrosis factor synthesis at separate points in the signaling pathway","volume":"172","author":"Han","year":"1990","journal-title":"J Exp Med"},{"key":"10.1016\/j.intimp.2009.01.013_bib29","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1046\/j.1365-2567.1997.00252.x","article-title":"Effect of lisofylline and pentoxifylline on the bacterial-stimulated production of TNF-alpha, IL-1 beta and IL-10 by human leucocytes","volume":"91","author":"van Furth","year":"1997","journal-title":"Immunology"},{"key":"10.1016\/j.intimp.2009.01.013_bib30","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1097\/00024382-199404000-00003","article-title":"CT-1501R selectively inhibits induced inflammatory monokines in human whole blood ex vivo","volume":"1","author":"Rice","year":"1994","journal-title":"Shock"},{"key":"10.1016\/j.intimp.2009.01.013_bib31","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1073\/pnas.91.9.3857","article-title":"Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid","volume":"91","author":"Rice","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.intimp.2009.01.013_bib32","first-page":"171","article-title":"Pentoxifylline increases survival in murine endotoxic shock and decreases formation of tumor necrosis factor","volume":"31","author":"Schade","year":"1990","journal-title":"Circ Shock"},{"key":"10.1016\/j.intimp.2009.01.013_bib33","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/jps.20257","article-title":"Pharmacodynamic interactions between recombinant mouse interleukin-10 and prednisolone using a mouse endotoxemia model","volume":"94","author":"Chakraborty","year":"2004","journal-title":"J Pharm Sci"},{"key":"10.1016\/j.intimp.2009.01.013_bib34","first-page":"192","article-title":"Pentoxifylline suppression of tumor necrosis factor gene transcription","volume":"110","author":"Doherty","year":"1991","journal-title":"Surg"},{"key":"10.1016\/j.intimp.2009.01.013_bib35","first-page":"14","article-title":"Potential role for phosphatidic acid in mediating the inflammatory responses to TNF-\u03b1 and IL-1\u03b2","volume":"44","author":"Bursten","year":"1994","journal-title":"Circ Shock"},{"key":"10.1016\/j.intimp.2009.01.013_bib36","first-page":"427","article-title":"Pentoxifylline inhibits endotoxin-induced NF-kappa B activation and associated production of proinflammatory cytokines","volume":"34","author":"Ji","year":"2004","journal-title":"Ann Clin Lab Sci"},{"key":"10.1016\/j.intimp.2009.01.013_bib37","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1196\/annals.1288.069","article-title":"Inhibition of STAT4 activation by lisofylline is associated with the protection of autoimmune diabetes","volume":"1005","author":"Yang","year":"2003","journal-title":"Ann NY Acad Sci"},{"key":"10.1016\/j.intimp.2009.01.013_bib38","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1128\/CDLI.6.4.594-598.1999","article-title":"Pentoxifylline inhibits superantigen-induced toxic shock and cytokine release","volume":"6","author":"Krakauer","year":"1999","journal-title":"Clin Diagn Lab Immunol."},{"key":"10.1016\/j.intimp.2009.01.013_bib39","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1172\/JCI200113763","article-title":"STAT4 and STAT6 regulate systemic inflammation and protect against lethal endotoxemia","volume":"108","author":"Lentsch","year":"2001","journal-title":"J Clin Invest"},{"key":"10.1016\/j.intimp.2009.01.013_bib40","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0014-2999(99)00265-4","article-title":"Pentoxifylline improves circulatory failure and survival in murine models of endotoxemia","volume":"373","author":"Wu","year":"1999","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.intimp.2009.01.013_bib41","first-page":"348","article-title":"Enhanced survival from cecal ligation and puncture with pentoxifylline is associated with altered neutrophil trafficking and reduced interleukin-1 beta expression but not inhibition of tumor necrosis factor synthesis","volume":"116","author":"Hadjiminas","year":"1994","journal-title":"Surg"},{"key":"10.1016\/j.intimp.2009.01.013_bib42","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/00003246-199901000-00038","article-title":"Effect of pentoxifylline on survival and intestinal cytokine messenger RNA transcription in a rat model of ongoing peritoneal sepsis","volume":"27","author":"Nelson","year":"1999","journal-title":"Crit Care Med"},{"key":"10.1016\/j.intimp.2009.01.013_bib43","first-page":"4342","article-title":"Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation","volume":"14","author":"Yamamoto","year":"1994","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.intimp.2009.01.013_bib44","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/chir.20299","article-title":"Interconversion and tissue distribution of pentoxifylline and lisofylline in mice","volume":"18","author":"Wyska","year":"2006","journal-title":"Chirality"},{"key":"10.1016\/j.intimp.2009.01.013_bib45","first-page":"193","article-title":"Protective action of calcium entry blockers in endotoxin shock","volume":"20","author":"Lee","year":"1986","journal-title":"Circ. Shock"},{"key":"10.1016\/j.intimp.2009.01.013_bib46","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1152\/ajpgi.1999.277.2.G351","article-title":"Effects of calcium channel antagonists on LPS-induced hepatic iNOS expression","volume":"277","author":"Mustafa","year":"1999","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.intimp.2009.01.013_bib47","doi-asserted-by":"crossref","first-page":"7735","DOI":"10.1073\/pnas.84.21.7735","article-title":"Cellular localization of the multidrug-resistance gene product, P-glycoprotein, in normal human tissues","volume":"84","author":"Thiebaut","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.intimp.2009.01.013_bib48","doi-asserted-by":"crossref","first-page":"3408","DOI":"10.1002\/art.20583","article-title":"Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action","volume":"50","author":"Buttgereit","year":"2004","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.intimp.2009.01.013_bib49","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1124\/dmd.104.001230","article-title":"The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the mdr1a\/1b knockout mouse model","volume":"33","author":"Doran","year":"2005","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.intimp.2009.01.013_bib50","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1211\/jpp.59.4.0003","article-title":"Pharmacokinetic modelling of pentoxifylline and lisofylline after oral and intravenous administration in mice","volume":"59","author":"Wyska","year":"2007","journal-title":"J Pharm Pharmacol"},{"key":"10.1016\/j.intimp.2009.01.013_bib51","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1006\/clin.1997.4420","article-title":"IL-6: insights into novel biological activities","volume":"85","author":"Barton","year":"1997","journal-title":"Clin Immunol Immunopathol"},{"key":"10.1016\/j.intimp.2009.01.013_bib52","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1182\/blood.V83.1.113.113","article-title":"Interleukin-6 as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55","volume":"83","author":"Tilg","year":"1994","journal-title":"Blood"},{"key":"10.1016\/j.intimp.2009.01.013_bib53","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1128\/iai.64.3.714-718.1996","article-title":"Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model","volume":"64","author":"Barton","year":"1996","journal-title":"Infect Immun"}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576909000289?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576909000289?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T17:04:40Z","timestamp":1761584680000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576909000289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,4]]}},"alternative-id":["S1567576909000289"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2009.01.013","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2009,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pretreatment with R(+)-verapamil significantly reduces mortality and cytokine expression in murine model of septic shock","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2009.01.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2009 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}