{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:44:19Z","timestamp":1760147059574,"version":"build-2065373602"},"reference-count":95,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union Horizon 2020 projects","award":["825828","952520","2020-1.1.6-J\u00d6V\u0150-2021-00013","K134939","BO\/00304\/20\/5","\u00daNKP-22-5\/202206201434KG"],"award-info":[{"award-number":["825828","952520","2020-1.1.6-J\u00d6V\u0150-2021-00013","K134939","BO\/00304\/20\/5","\u00daNKP-22-5\/202206201434KG"]}]},{"name":"National Research, Development, and Innovation Office (NKFIH) of Hungary","award":["825828","952520","2020-1.1.6-J\u00d6V\u0150-2021-00013","K134939","BO\/00304\/20\/5","\u00daNKP-22-5\/202206201434KG"],"award-info":[{"award-number":["825828","952520","2020-1.1.6-J\u00d6V\u0150-2021-00013","K134939","BO\/00304\/20\/5","\u00daNKP-22-5\/202206201434KG"]}]},{"name":"Bolyai Scholarship of the Hungarian Academy of Sciences","award":["825828","952520","2020-1.1.6-J\u00d6V\u0150-2021-00013","K134939","BO\/00304\/20\/5","\u00daNKP-22-5\/202206201434KG"],"award-info":[{"award-number":["825828","952520","2020-1.1.6-J\u00d6V\u0150-2021-00013","K134939","BO\/00304\/20\/5","\u00daNKP-22-5\/202206201434KG"]}]},{"name":"\u00daNKP Bolyai+ Scholarship from the Hungarian Ministry of Innovation and Technology and National Research, Development, and Innovation Office","award":["825828","952520","2020-1.1.6-J\u00d6V\u0150-2021-00013","K134939","BO\/00304\/20\/5","\u00daNKP-22-5\/202206201434KG"],"award-info":[{"award-number":["825828","952520","2020-1.1.6-J\u00d6V\u0150-2021-00013","K134939","BO\/00304\/20\/5","\u00daNKP-22-5\/202206201434KG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hemodynamic disturbance, a rise in neutrophil-to-lymphocyte ratio (NLR) and release of inflammatory cytokines into blood, is a bad prognostic indicator in severe COVID-19 and other diseases involving cytokine storm syndrome (CSS). The purpose of this study was to explore if zymosan, a known stimulator of the innate immune system, could reproduce these changes in pigs. Pigs were instrumented for hemodynamic analysis and, after i.v. administration of zymosan, serial blood samples were taken to measure blood cell changes, cytokine gene transcription in PBMC and blood levels of inflammatory cytokines, using qPCR and ELISA. Zymosan bolus (0.1 mg\/kg) elicited transient hemodynamic disturbance within minutes without detectable cytokine or blood cell changes. In contrast, infusion of 1 mg\/kg zymosan triggered maximal pulmonary hypertension with tachycardia, lasting for 30 min. This was followed by a transient granulopenia and then, up to 6 h, major granulocytosis, resulting in a 3\u20134-fold increase in NLR. These changes were paralleled by massive transcription and\/or rise in IL-6, TNF-alpha, CCL-2, CXCL-10, and IL-1RA in blood. There was significant correlation between lymphopenia and IL-6 gene expression. We conclude that the presented model may enable mechanistic studies on late-stage COVID-19 and CSS, as well as streamlined drug testing against these conditions.<\/jats:p>","DOI":"10.3390\/ijms24021138","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T01:36:17Z","timestamp":1673228177000},"page":"1138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Zymosan Particle-Induced Hemodynamic, Cytokine and Blood Cell Changes in Pigs: An Innate Immune Stimulation Model with Relevance to Cytokine Storm Syndrome and Severe COVID-19"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0345-6914","authenticated-orcid":false,"given":"G\u00e1bor","family":"K\u00f6k\u00e9ny","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"},{"name":"International Nephrology Research and Training Center, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"Bakos","sequence":"additional","affiliation":[{"name":"Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1lint Andr\u00e1s","family":"Barta","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina Vikt\u00f3ria","family":"Nagy","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"M\u00e9sz\u00e1ros","sequence":"additional","affiliation":[{"name":"Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"},{"name":"SeroScience Ltd., 1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gergely T.","family":"Kozma","sequence":"additional","affiliation":[{"name":"Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"},{"name":"SeroScience Ltd., 1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e1s","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"2nd Department of Pediatrics, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1nos","family":"Szebeni","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"},{"name":"Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"},{"name":"SeroScience Ltd., 1089 Budapest, Hungary"},{"name":"Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health Sciences, Miskolc University, 2880 Miskolc, Hungary"},{"name":"Translational Nanobioscience Research Center, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9la","family":"Merkely","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"Radovits","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.3389\/fimmu.2020.01708","article-title":"Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies","volume":"11","author":"Tang","year":"2020","journal-title":"Front. 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