{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T11:45:57Z","timestamp":1778759157076,"version":"3.51.4"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Microbial Pathogenesis"],"published-print":{"date-parts":[[2022,12]]},"DOI":"10.1016\/j.micpath.2022.105786","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T11:44:50Z","timestamp":1663674290000},"page":"105786","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"PA","title":["Anti-macrophage migration inhibitory factor (MIF) activity of ibudilast: A repurposing drug attenuates the pathophysiology of leptospirosis"],"prefix":"10.1016","volume":"173","author":[{"given":"Krishnamoorthi","family":"Sumaiya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panneerselvam","family":"Selvambika","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7805-2666","authenticated-orcid":false,"given":"Kalimuthusamy","family":"Natarajaseenivasan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.micpath.2022.105786_bib1","first-page":"65","article-title":"Leptospirosis in humans","volume":"387","author":"Haake","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"10.1016\/j.micpath.2022.105786_bib2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S1473-3099(03)00830-2","article-title":"Leptospirosis: a zoonotic disease of global importance","volume":"3","author":"Bharti","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.micpath.2022.105786_bib3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003898","article-title":"Global morbidity and mortality of leptospirosis: a systematic review","volume":"9","author":"Costa","year":"2015","journal-title":"PLoS Neglected Trop. Dis."},{"key":"10.1016\/j.micpath.2022.105786_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004039","article-title":"Leptospirosis: updating the global picture of an emerging neglected disease","volume":"9","author":"Picardeau","year":"2015","journal-title":"PLoS Neglected Trop. Dis."},{"key":"10.1016\/j.micpath.2022.105786_bib5","series-title":"Treasure Island (FL)","article-title":"Leptospirosis","author":"Wang","year":"2022"},{"key":"10.1016\/j.micpath.2022.105786_bib6","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/365756a0","article-title":"MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia","volume":"365","author":"Bernhagen","year":"1993","journal-title":"Nature"},{"key":"10.1016\/j.micpath.2022.105786_bib7","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1158\/1535-7163.MCT-12-0988","article-title":"Human anti-macrophage migration inhibitory factor antibodies inhibit growth of human prostate cancer cells in vitro and in vivo","volume":"12","author":"Hussain","year":"2013","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.micpath.2022.105786_bib8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1089\/hyb.2008.0069","article-title":"Characterization and application of two novel monoclonal antibodies against human CXCR4: cell proliferation and migration regulation for glioma cell line in vitro by CXCR4\/SDF-1alpha signal","volume":"28","author":"Cheng","year":"2009","journal-title":"Hybridoma (Larchmt)"},{"key":"10.1016\/j.micpath.2022.105786_bib9","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1158\/1078-0432.CCR-12-2333","article-title":"BMS-936564\/MDX-1338: a fully human anti-CXCR4 antibody induces apoptosis in vitro and shows antitumor activity in vivo in hematologic malignancies","volume":"19","author":"Kuhne","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.micpath.2022.105786_bib10","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.canlet.2005.10.041","article-title":"Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis","volume":"241","author":"Wente","year":"2006","journal-title":"Cancer Lett."},{"key":"10.1016\/j.micpath.2022.105786_bib11","doi-asserted-by":"crossref","first-page":"9074","DOI":"10.1523\/JNEUROSCI.1238-10.2010","article-title":"Myelin repair is accelerated by inactivating CXCR2 on nonhematopoietic cells","volume":"30","author":"Liu","year":"2010","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"10.1016\/j.micpath.2022.105786_bib12","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/j.1582-4934.2010.01041.x","article-title":"Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment","volume":"15","author":"Simons","year":"2011","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.micpath.2022.105786_bib13","first-page":"3411","article-title":"Novel half-life extended anti-MIF nanobodies protect against endotoxic shock","volume":"32","author":"Sparkes","year":"2018","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"10.1016\/j.micpath.2022.105786_bib14","doi-asserted-by":"crossref","first-page":"7446","DOI":"10.1074\/jbc.M111.329664","article-title":"Neutralization of macrophage migration inhibitory factor (MIF) by fully human antibodies correlates with their specificity for the \u03b2-sheet structure of MIF*","volume":"287","author":"Kerschbaumer","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.micpath.2022.105786_bib15","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1200\/jco.2015.33.15_suppl.2518","article-title":"First-in-human, phase I study assessing imalumab (Bax69), a first-in-class anti-oxidized macrophage migration inhibitory factor (oxMIF) antibody in advanced solid tumors","volume":"33","author":"Mahalingam","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.micpath.2022.105786_bib16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4155\/fmc.10.281","article-title":"MIF as a disease target: ISO-1 as a proof-of-concept therapeutic","volume":"3","author":"Al-Abed","year":"2011","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.micpath.2022.105786_bib17","doi-asserted-by":"crossref","first-page":"11313","DOI":"10.1073\/pnas.1002716107","article-title":"Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast","volume":"107","author":"Cho","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.micpath.2022.105786_bib18","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1073\/pnas.011569399","article-title":"Inhibition of macrophage migration inhibitory factor (MIF) tautomerase and biological activities by acetaminophen metabolites","volume":"99","author":"Senter","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.micpath.2022.105786_bib19","doi-asserted-by":"crossref","first-page":"7253","DOI":"10.1158\/0008-5472.CAN-07-6227","article-title":"A novel, macrophage migration inhibitory factor suicide substrate inhibits motility and growth of lung cancer cells","volume":"68","author":"Winner","year":"2008","journal-title":"Cancer Res."},{"key":"10.1016\/j.micpath.2022.105786_bib20","doi-asserted-by":"crossref","first-page":"30653","DOI":"10.1074\/jbc.M112.385583","article-title":"A novel allosteric inhibitor of macrophage migration inhibitory factor (MIF)","volume":"287","author":"Bai","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.micpath.2022.105786_bib21","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1093\/carcin\/bgt239","article-title":"Macrophage migratory inhibitory factor promotes bladder cancer progression via increasing proliferation and angiogenesis","volume":"34","author":"Choudhary","year":"2013","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.micpath.2022.105786_bib22","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.drudis.2018.06.017","article-title":"Small-molecule inhibitors of macrophage migration inhibitory factor (MIF) as an emerging class of therapeutics for immune disorders","volume":"23","author":"Kok","year":"2018","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.micpath.2022.105786_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2021.128445","article-title":"Repurposing old drugs as novel inhibitors of human MIF from structural and functional analysis","volume":"55","author":"Yang","year":"2022","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.micpath.2022.105786_bib24","first-page":"1516","article-title":"Inactivation of tautomerase activity of macrophage migration inhibitory factor by sulforaphane: a potential biomarker for anti-inflammatory intervention","volume":"20","author":"Healy","year":"2011","journal-title":"Cancer Epidemiol. Biomarkers Prev. a Publ. Am. Assoc. Cancer Res. Cosponsored by Am. Soc. Prev. Oncol."},{"key":"10.1016\/j.micpath.2022.105786_bib25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ejmech.2016.09.020","article-title":"Discovery of 6, 7-dihydro-3H-pyrano [4, 3-c] isoxazol-3-ones as a new class of pathogen specific anti-leptospiral agents","volume":"125","author":"Ilangovan","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.micpath.2022.105786_bib26","doi-asserted-by":"crossref","first-page":"89869","DOI":"10.1039\/C5RA15060D","article-title":"Dietary flavone chrysin (5, 7-dihydroxyflavone ChR) functionalized highly-stable metal nanoformulations for improved anticancer applications","volume":"5","author":"Sathishkumar","year":"2015","journal-title":"RSC Adv."},{"key":"10.1016\/j.micpath.2022.105786_bib27","first-page":"1607","article-title":"MIF rediscovered: cytokine, pituitary hormone, and glucocorticoid-induced regulator of the immune response","volume":"10","author":"Bucala","year":"1996","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"10.1016\/j.micpath.2022.105786_bib28","article-title":"Macrophage migration inhibitory factor (MIF): a multifaceted cytokine regulated by genetic and physiological strategies","author":"Sumaiya","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.micpath.2022.105786_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2021.108024","article-title":"Macrophage migration inhibitory factor (MIF): a multifaceted cytokine regulated by genetic and physiological strategies","volume":"233","author":"Sumaiya","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.micpath.2022.105786_bib30","doi-asserted-by":"crossref","first-page":"8104","DOI":"10.1021\/acs.jmedchem.8b00589","article-title":"Advances and insights for small molecule inhibition of macrophage migration inhibitory factor","volume":"61","author":"Trivedi-Parmar","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.micpath.2022.105786_bib31","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1093\/oxfordjournals.jbchem.a021844","article-title":"Substrate specificity for isomerase activity of macrophage migration inhibitory factor and its inhibition by indole derivatives","volume":"122","author":"Suzuki","year":"1997","journal-title":"J. Biochem."},{"key":"10.1016\/j.micpath.2022.105786_bib32","doi-asserted-by":"crossref","first-page":"24976","DOI":"10.1074\/jbc.M203220200","article-title":"The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents","volume":"277","author":"Lubetsky","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.micpath.2022.105786_bib33","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1096\/fj.10-162347","article-title":"A small\u2010molecule inhibitor of macrophage migration inhibitory factor for the treatment of inflammatory disease","volume":"24","author":"Kithcart","year":"2010","journal-title":"Faseb. J."},{"key":"10.1016\/j.micpath.2022.105786_bib34","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.3892\/ijo.2014.2551","article-title":"ISO-66, a novel inhibitor of macrophage migration, shows efficacy in melanoma and colon cancer models","volume":"45","author":"Ioannou","year":"2014","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.micpath.2022.105786_bib35","doi-asserted-by":"crossref","first-page":"7033","DOI":"10.1016\/j.bmcl.2010.09.118","article-title":"Receptor agonists of macrophage migration inhibitory factor","volume":"20","author":"Jorgensen","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.micpath.2022.105786_bib36","doi-asserted-by":"crossref","first-page":"26581","DOI":"10.1074\/jbc.M110.113951","article-title":"Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action","volume":"285","author":"Ouertatani-Sakouhi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.micpath.2022.105786_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109704","article-title":"Molecular mechanisms and clinical application of Iguratimod: a review","volume":"122","author":"Jiang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.micpath.2022.105786_bib38","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.freeradbiomed.2020.06.032","article-title":"Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections","volume":"156","author":"Sies","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.micpath.2022.105786_bib39","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1517\/14656560903426189","article-title":"Ibudilast: a review of its pharmacology, efficacy and safety in respiratory and neurological disease","volume":"10","author":"Rolan","year":"2009","journal-title":"Expet Opin. Pharmacother."},{"key":"10.1016\/j.micpath.2022.105786_bib40","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1111\/j.1365-2125.2008.03270.x","article-title":"Ibudilast in healthy volunteers: safety, tolerability and pharmacokinetics with single and multiple doses","volume":"66","author":"Rolan","year":"2008","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.micpath.2022.105786_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.drugalcdep.2019.107776","article-title":"Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder","volume":"206","author":"Li","year":"2020","journal-title":"Drug Alcohol Depend."},{"key":"10.1016\/j.micpath.2022.105786_bib42","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2021.677999","article-title":"Inflammatory signatures of pathogenic and non-pathogenic Leptospira infection in susceptible C3H-HeJ mice","volume":"11","author":"Shetty","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.micpath.2022.105786_bib43","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0035-9203(00)90445-0","article-title":"Pulmonary haemorrhage as a predominant cause of death in leptospirosis in Seychelles","volume":"94","author":"Yersin","year":"2000","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"10.1016\/j.micpath.2022.105786_bib44","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1590\/S1413-86702007000100029","article-title":"Pathology and pathophysiology of pulmonary manifestations in leptospirosis","volume":"11","author":"Dolhnikoff","year":"2007","journal-title":"Braz. J. Infect. Dis."},{"key":"10.1016\/j.micpath.2022.105786_bib45","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1742-2094-2-10","article-title":"Anti-inflammatory therapy by ibudilast, a phosphodiesterase inhibitor, in demyelination of twitcher, a genetic demyelination model","volume":"2","author":"Kagitani-Shimono","year":"2005","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.micpath.2022.105786_bib46","article-title":"Ibudilast attenuates folic acid\u2013induced acute kidney injury by blocking pyroptosis through TLR4-mediated NF-\u03baB and MAPK signaling pathways","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.micpath.2022.105786_bib47","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.810834","article-title":"Necroptosis contributes to persistent inflammation during acute leptospirosis","volume":"13","author":"Kundu","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.micpath.2022.105786_bib48","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1002\/1529-0131(200112)44:12<2862::AID-ART474>3.0.CO;2-W","article-title":"Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides","volume":"44","author":"Mohan","year":"2001","journal-title":"Arthritis Rheum."},{"key":"10.1016\/j.micpath.2022.105786_bib49","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/00054725-200401000-00004","article-title":"Demyelination during anti-tumor necrosis factor alpha therapy with infliximab for Crohn's disease","volume":"10","author":"Thomas","year":"2004","journal-title":"Inflamm. Bowel Dis."}],"container-title":["Microbial Pathogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0882401022003990?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0882401022003990?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:41:39Z","timestamp":1760110899000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0882401022003990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":49,"alternative-id":["S0882401022003990"],"URL":"https:\/\/doi.org\/10.1016\/j.micpath.2022.105786","relation":{},"ISSN":["0882-4010"],"issn-type":[{"value":"0882-4010","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Anti-macrophage migration inhibitory factor (MIF) activity of ibudilast: A repurposing drug attenuates the pathophysiology of leptospirosis","name":"articletitle","label":"Article Title"},{"value":"Microbial Pathogenesis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.micpath.2022.105786","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"105786"}}