{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:47:17Z","timestamp":1789073237474,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The clinical effectiveness of Oxiris\u00ae, particularly in reducing cytokines, remains uncertain due to the limited data provided. This study explored and analyzed the application value of Oxiris\u00ae endotoxin adsorption technology in a large animal model. Pigs received an intravenous LPS infusion. Six animals were treated 2 h after the infusion with an Oxiris\u00ae hemadsorption using a pumpless extracorporeal technique for 6 h. Five animals served as controls. Cardiocirculatory parameters, hyperspectral analysis, and a panel of cytokines were measured. The lipopolysaccharide infusion induced sepsis-like inflammation with tachycardia, elevated pulmonary pressure, elevated lactate level, as well as elevated pro-inflammatory cytokines like interferon (IFN)-\u03b3, interleukin (IL)-1\u03b2, IL-2, IL-6, IL-8, IL-12 and tumor necrosis factor alpha (TNF-\u03b1). In addition, increases of anti-inflammatory cytokines like IL-1ra and IL-10 were found. After 3 and 6 h in both groups, pro-inflammatory cytokines were significantly reduced. No differences between the intervention and the control group could be detected after 3 and 6 h for IL-1\u03b2, IL-2, IL-6, IL-8, IL-12 and TNF-\u03b1, suggesting no effect of the Oxiris\u00ae filter on the elimination of elevated cytokines with a pumpless extracorporeal hemadsorption technique. The presented large animal model may be a promising option for studying the effects of hemadsorption techniques.<\/jats:p>","DOI":"10.3390\/ijms25179283","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T09:26:51Z","timestamp":1724750811000},"page":"9283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of Oxiris\u00ae Therapy on Cytokine Elimination after a LPS Infusion\u2014An Experimental Animal Study"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3394-481X","authenticated-orcid":false,"given":"Armin","family":"Kalenka","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"},{"name":"Hospital Bergstrasse, 64646 Heppenheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Arens","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf M.","family":"M\u00fcllenbach","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care Medicine, Emergency Medicine and Pain Therapy, ECMO-Center, Campus Kassel of the University of Southampton, 34125 Kassel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"Brune","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Clinical Chemistry, Medical Faculty, University Hospital Heidelberg, University Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-2783","authenticated-orcid":false,"given":"Mascha O.","family":"Fiedler-Kalenka","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1056\/NEJMoa022139","article-title":"The epidemiology of sepsis in the United States from 1979 through 2000","volume":"348","author":"Martin","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Beltr\u00e1n-Garc\u00eda, J., Osca-Verdegal, R., J\u00e1vega, B., Herrera, G., O\u2019Connor, J.E., Garc\u00eda-L\u00f3pez, E., Casab\u00f3-Vall\u00e9s, G., Rodriguez-Gimillo, M., Ferreres, J., and Carbonell, N. (2022). Characterization of Early Peripheral Immune Responses in Patients with Sepsis and Septic Shock. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030525"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"306","DOI":"10.2174\/1389557510909030306","article-title":"New insight in LPS antagonist","volume":"9","author":"Ianaro","year":"2009","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e62270","DOI":"10.7554\/eLife.62270","article-title":"The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline","volume":"10","author":"Janosevic","year":"2021","journal-title":"eLife"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hellman, T., Uusalo, P., and J\u00e4rvisalo, M.J. (2021). Renal Replacement Techniques in Septic Shock. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910238"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Berlot, G., Tomasini, A., Zanchi, S., and Moro, E. (2023). The Techniques of Blood Purification in the Treatment of Sepsis and Other Hyperinflammatory Conditions. J. Clin. Med., 12.","DOI":"10.3390\/jcm12051723"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000499520","article-title":"Extracorporeal Blood Purification Therapies for Sepsis","volume":"47","author":"Monard","year":"2019","journal-title":"Blood Purif."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40635-018-0177-2","article-title":"In vitro comparison of the adsorption of inflammatory mediators by blood purification devices","volume":"6","author":"Malard","year":"2018","journal-title":"Intensive Care Med. Exp."},{"key":"ref_9","first-page":"421","article-title":"High-volume haemofiltration with a new haemofiltration membrane having enhanced adsorption properties in septic pigs","volume":"24","author":"Assadi","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"154844","DOI":"10.1016\/j.jcrc.2024.154844","article-title":"Outcomes of extracorporeal blood purification with oXiris\u00ae membrane in critically ill patients: A systematic review and meta-analysis","volume":"83","author":"Siew","year":"2024","journal-title":"J. Crit. Care"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fiedler, M.O., Muellenbach, R.M., Rolfes, C., Lotz, C., Nickel, F., M\u00fcller-Stich, B.P., Supady, A., Lepper, P.M., Weigand, M.A., and Meybohm, P. (2022). Pumpless Extracorporeal Hemadsorption Technique (pEHAT): A Proof-of-Concept Animal Study. J. Clin. Med., 11.","DOI":"10.3390\/jcm11226815"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.tim.2011.11.002","article-title":"The pig: A model for human infectious diseases","volume":"20","author":"Meurens","year":"2012","journal-title":"Trends Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vintrych, P., Al-Obeidallah, M., Hor\u00e1k, J., Chvojka, J., Vale\u0161ov\u00e1, L., Nalos, L., Jarkovsk\u00e1, D., Mat\u011bjovi\u010d, M., and \u0160tengl, M. (2022). Modeling sepsis, with a special focus on large animal models of porcine peritonitis and bacteremia. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.1094199"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/SHK.0b013e318181a343","article-title":"Experimental models of sepsis and their clinical relevance","volume":"30","author":"Garrido","year":"2008","journal-title":"Shock"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.vetimm.2015.06.001","article-title":"In vivo porcine lipopolysaccharide inflammation models to study immunomodulation of drugs","volume":"166","author":"Wyns","year":"2015","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/0022-4804(90)90260-9","article-title":"Laboratory models of sepsis and septic shock","volume":"49","author":"Fink","year":"1990","journal-title":"J. Surg. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.vetimm.2005.04.014","article-title":"Acute feed intake and acute-Phase protein responses following a lipopolysaccharide challenge in pigs from two dam lines","volume":"107","author":"Frank","year":"2005","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.domaniend.2005.03.009","article-title":"Evaluation of the acute phase response in cloned pigs following a lipopolysaccharide challenge","volume":"29","author":"Carroll","year":"2005","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.domaniend.2009.04.004","article-title":"Temporal pattern and effect of sex on lipopolysaccharide-induced stress hormone and cytokine response in pigs","volume":"37","author":"Williams","year":"2009","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Urmann, A., Mohnke, K., Riedel, J., Hain, J., Renz, M., Rissel, R., Duenges, B., Ruemmler, R., and Ziebart, A. (2023). Lipopolysaccharide Infusion as a Porcine Endotoxemic Shock Model. J. Vis. Exp., 66039.","DOI":"10.3791\/66039"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000096970","article-title":"Age-related changes in pro-inflammatory cytokines, acute phase proteins and cortisol concentrations in neonatal piglets","volume":"91","author":"Boyle","year":"2007","journal-title":"Neonatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.vetimm.2012.09.041","article-title":"Development of a cytometric bead array screening tool for the simultaneous detection of pro-inflammatory cytokines in porcine plasma","volume":"151","author":"Wyns","year":"2013","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Castegren, M., Skorup, P., Lipcsey, M., Larsson, A., and Sj\u00f6lin, J. (2013). Endotoxin tolerance variation over 24 h during porcine endotoxemia: Association with changes in circulation and organ dysfunction. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053221"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Broman, M.E., Hansson, F., Vincent, J.L., and Bodelsson, M. (2019). Endotoxin and cytokine reducing properties of the oXiris membrane in patients with septic shock: A randomized crossover double-blind study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220444"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1186\/s13054-021-03830-z","article-title":"Changes in carbon dioxide production and oxygen uptake evaluated using indirect calorimetry in mechanically ventilated patients with sepsis","volume":"25","author":"Hirayama","year":"2021","journal-title":"Crit. Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ccm.2016.01.011","article-title":"Metabolism, Metabolomics, and Nutritional Support of Patients with Sepsis","volume":"37","author":"Englert","year":"2016","journal-title":"Clin. Chest Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kuhlmann, H., Garczarek, L., K\u00fcnne, D., Pattberg, K., Skarabis, A., Frank, M., Schmidt, B., Arends, S., Herbstreit, F., and Brenner, T. (2023). Bedside Hyperspectral Imaging and Organ Dysfunction Severity in Critically Ill COVID-19 Patients-A Prospective, Monocentric Observational Study. Bioengineering, 10.","DOI":"10.3390\/bioengineering10101167"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1001\/jama.2018.14618","article-title":"Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial","volume":"320","author":"Dellinger","year":"2018","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sch\u00e4dler, D., Pausch, C., Heise, D., Meier-Hellmann, A., Brederlau, J., Weiler, N., Marx, G., Putensen, C., Spies, C., and J\u00f6rres, A. (2017). The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187015"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13054-017-1662-9","article-title":"Hemoadsorption by CytoSorb in septic patients: A case series","volume":"21","author":"Kogelmann","year":"2017","journal-title":"Crit. Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13054-023-04391-z","article-title":"CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo","volume":"27","author":"Jansen","year":"2023","journal-title":"Crit. Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/SHK.0000000000000439","article-title":"Evaluation of the Cytosorb\u2122 Hemoadsorptive Column in a Pig Model of Severe Smoke and Burn Injury","volume":"44","author":"Linden","year":"2015","journal-title":"Shock"},{"key":"ref_33","first-page":"161","article-title":"Cytokines in the systemic inflammatory response syndrome: A review","volume":"2","author":"Jaffer","year":"2010","journal-title":"HSR Proc. Intensive Care Cardiovasc. Anesth."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/s13054-023-04555-x","article-title":"Continuous renal replacement therapy with the adsorptive oXiris filter may be associated with the lower 28-day mortality in sepsis: A systematic review and meta-analysis","volume":"27","author":"Wang","year":"2023","journal-title":"Crit. Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1159\/000519166","article-title":"Comparison of the Clinical Effectiveness of AN69-oXiris versus AN69-ST Filter in Septic Patients: A Single-Centre Study","volume":"51","author":"Zang","year":"2022","journal-title":"Blood Purif."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Guan, M., Wang, H., Tang, X., Zhao, Y., Wang, F., Zhang, L., and Fu, P. (2022). Continuous Renal Replacement Therapy With Adsorbing Filter oXiris in Acute Kidney Injury With Septic Shock: A Retrospective Observational Study. Front. Med., 9.","DOI":"10.3389\/fmed.2022.789623"},{"key":"ref_37","first-page":"3839","article-title":"The application value of oXiris-endotoxin adsorption in sepsis","volume":"13","author":"Zhai","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1159\/000074937","article-title":"Extracorporeal therapies in non-renal disease: Treatment of sepsis and the peak concentration hypothesis","volume":"22","author":"Ronco","year":"2004","journal-title":"Blood Purif."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1681\/ASN.V104846","article-title":"Cytokine removal during continuous hemofiltration in septic patients","volume":"10","author":"Colardyn","year":"1999","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s001340050330","article-title":"Cytokine removal and cardiovascular hemodynamics in septic patients with continuous venovenous hemofiltration","volume":"23","author":"Heering","year":"1997","journal-title":"Intensive Care Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1440-1797.2006.00600.x","article-title":"Serum IL-6 and IL-1-ra with sequential organ failure assessment scores in septic patients receiving high-volume haemofiltration and continuous venovenous haemofiltration","volume":"11","author":"Ghani","year":"2006","journal-title":"Nephrology"},{"key":"ref_42","first-page":"104","article-title":"Pharmacological treatment of COVID-19: Narrative review of the Working Group in Infectious Diseases and Sepsis (GTEIS) and the Working Groups in Transfusions and Blood Products (GTTH)","volume":"45","author":"Escapa","year":"2021","journal-title":"Med. Intensiva"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1097\/SHK.0000000000002223","article-title":"Clinical utility of interleukin-1 inhibitors in pediatric sepsis","volume":"61","author":"Manchikalapati","year":"2024","journal-title":"Shock"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dietrich, M., \u00d6zdemir, B., Gruneberg, D., Petersen, C., Studier-Fischer, A., von der Forst, M., Schmitt, F.C.F., Fiedler, M.O., Nickel, F., and M\u00fcller-Stich, B.P. (2021). Hyperspectral Imaging for the Evaluation of Microcirculatory Tissue Oxygenation and Perfusion Quality in Haemorrhagic Shock: A Porcine Study. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121829"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"156296","DOI":"10.1016\/j.cyto.2023.156296","article-title":"Predicting cytokine kinetics during sepsis; a modelling framework from a porcine sepsis model with live Escherichia coli","volume":"169","author":"Bahnasawy","year":"2023","journal-title":"Cytokine"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Thorsted, A., Bouchene, S., Tano, E., Castegren, M., Lipcsey, M., Sj\u00f6lin, J., Karlsson, M.O., Friberg, L.E., and Nielsen, E.I. (2019). A non-linear mixed effect model for innate immune response: In vivo kinetics of endotoxin and its induction of the cytokines tumor necrosis factor alpha and interleukin-6. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211981"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Fardisi, M., Thelen, K., Groenendal, A., Rajput, M., Sebastian, K., Contreras, G.A., and Moeser, A.J. (2023). Early weaning and biological sex shape long-term immune and metabolic responses in pigs. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-42553-9"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9283\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:43:33Z","timestamp":1760111013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,27]]},"references-count":47,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179283"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179283","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,27]]}}}