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High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50\u00a0mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65\u201375\u00a0mmHg for 12\u00a0h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (<jats:sup>99m<\/jats:sup>technetium albumin). cDPP3 activity, equilibrium analysis of the renin\u2013angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO<jats:sub>2<\/jats:sub>\/FiO<jats:sub>2<\/jats:sub> ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s40635-024-00638-3","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T16:02:30Z","timestamp":1717776150000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Inhibition of circulating dipeptidyl-peptidase 3 by procizumab in experimental septic shock reduces catecholamine exposure and myocardial injury"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-1594","authenticated-orcid":false,"given":"Bruno","family":"Garcia","sequence":"first","affiliation":[]},{"given":"Benoit","family":"ter Schiphorst","sequence":"additional","affiliation":[]},{"given":"Karine","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Fuhong","family":"Su","sequence":"additional","affiliation":[]},{"given":"Laurence","family":"Dewachter","sequence":"additional","affiliation":[]},{"given":"Francisco","family":"Vasques-N\u00f3voa","sequence":"additional","affiliation":[]},{"given":"Estela","family":"Rocha-Oliveira","sequence":"additional","affiliation":[]},{"suffix":"Jr.","given":"Roberto","family":"Roncon-Albuquerque","sequence":"additional","affiliation":[]},{"given":"Theo","family":"Uba","sequence":"additional","affiliation":[]},{"given":"Oliver","family":"Hartmann","sequence":"additional","affiliation":[]},{"given":"Adrien","family":"Picod","sequence":"additional","affiliation":[]},{"given":"Feriel","family":"Azibani","sequence":"additional","affiliation":[]},{"given":"Jacques","family":"Callebert","sequence":"additional","affiliation":[]},{"given":"Serge","family":"Goldman","sequence":"additional","affiliation":[]},{"given":"Filippo","family":"Annoni","sequence":"additional","affiliation":[]},{"given":"Rapha\u00ebl","family":"Favory","sequence":"additional","affiliation":[]},{"given":"Jean-Louis","family":"Vincent","sequence":"additional","affiliation":[]},{"given":"Jacques","family":"Creteur","sequence":"additional","affiliation":[]},{"given":"Fabio Silvio","family":"Taccone","sequence":"additional","affiliation":[]},{"given":"Alexandre","family":"Mebazaa","sequence":"additional","affiliation":[]},{"given":"Antoine","family":"Herpain","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"638_CR1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour CW et al (2016) The third international consensus definitions for sepsis and septic shock (Sepsis-3). 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Experiments were performed in the Experimental Laboratory of Intensive Care of the ULB (LA1230406).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"B.G. was supported by a grant from Universit\u00e9 Libre de Bruxelles (ULB), Belgium. B.T.S was supported by a grant from \u201cAnn\u00e9e recherche, relations internationals\u201d, UFR3S, Universit\u00e9 de Lille, France. K.S., T.I.U and O.H. are employed by 4TEEN4 Pharmaceuticals.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"53"}}