Specificity of Presepsin as a Biomarker of Bacterial Infection in Mouse Sepsis Models

Published:November 25, 2022DOI:


      • Presepsin (P-SEP) was first discovered in 2002; however, there have been no reports on serum P-SEP level in mice.
      • This study used a P-SEP enzyme-linked immunosorbent assay kit to evaluate the changes in serum P-SEP level in mouse sepsis models compared with other inflammatory markers.
      • Serum P-SEP levels increased earlier than other inflammatory markers in the mouse cecal ligation and puncture model. In contrast, serum P-SEP levels were not elevated in the CL and LPS-induced sepsis models.
      • Mouse P-SEP is elevated early in infection and more specific to bacterial infection compared with other biomarkers.



      Since its discovery in 2002, presepsin (P-SEP) has been reported to be useful in the early diagnosis of sepsis and has been evaluated in many clinical studies. However, as antibodies that bind to mouse P-SEP were previously unavailable, serum P-SEP levels in mice are limited. This study used a P-SEP enzyme-linked immunosorbent assay kit to evaluate the changes in serum P-SEP levels in mouse sepsis models compared with changes in other inflammatory markers and determine whether P-SEP can function as a biomarker specific to bacterial infections.


      Sepsis was induced in mice via cecal ligation and puncture (CLP), induction with lipopolysaccharide (LPS), and cecal ligation (CL) model was created as a control for the CLP model, following which clinical biomarkers (P-SEP, C-reactive protein, and procalcitonin) were evaluated.


      The 48-h survival rates in the CLP, CL, and LPS-induced sepsis models were 67%, 89%, and 57%, respectively. Serum C-reactive protein levels did not increase in the CLP and CL models within 24 h but significantly increased in the LPS-induced sepsis model. Serum procalcitonin levels increased in the CLP and CL models and especially increased in the LPS-induced sepsis model. In contrast, an increase in serum P-SEP level was found in the CLP model at 6 h compared with those at baseline, the CL, and LPS-induced sepsis models.


      Mouse P-SEP is elevated early in infection and more specific to bacterial infection compared with other biomarkers.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Rudiger A.
        • Stotz M.
        • Singer M.
        Cellular processes in sepsis.
        Swiss Med Wkly. 2008; 138: 629-634
        • Dellinger R.P.
        • Levy M.M.
        • Rhodes A.
        • et al.
        Surviving sepsis Campaign guidelines committee including the pediatric subgroup: surviving sepsis Campaign: international guidelines for management of severe sepsis and septic shock.
        Intensive Care Med. 2012; 39: 165-228
        • Riedel S.
        • Melendez J.H.
        • An A.T.
        • et al.
        Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department.
        Am J Clin Pathol. 2011; 135: 182-189
        • Kumar A.
        • Roberts D.
        • Wood K.E.
        • et al.
        Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.
        Crit Care Med. 2006; 34: 1589-1596
        • Rhodes A.
        • Evans L.E.
        • Alhazzani W.
        • et al.
        Surviving sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016.
        Intensive Care Med. 2017; 43: 304-377
        • Levy M.M.
        • Evans L.E.
        • Rhodes A.
        The surviving sepsis campaign bundle: 2018 update.
        Intensive Care Med. 2018; 44: 925-928
        • Gaïni S.
        • Koldkjaer O.G.
        • Pedersen C.
        • et al.
        Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study.
        Crit Care. 2006; 10: R53
        • Jekarl D.W.
        • Lee S.Y.
        • Lee J.
        • et al.
        Procalcitonin as a diagnostic Marker and IL-6 as a prognostic marker for sepsis.
        Diagn Microbiol Infect Dis. 2013; 75: 342-347
        • Meisner M.
        • Adina H.
        • Schmidt J.
        Correlation of procalcitonin and C-reactive protein to inflammation, complications, and outcome during the intensive care unit course of multiple-trauma patients.
        Crit Care. 2006; 10: R1
        • Nylen E.S.
        • O’Neill W.
        • Jordan M.H.
        • et al.
        Serum procalcitonin as an index of inhalation injury in burns.
        Horm Metab Res. 1992; 24: 439-443
        • Ammori B.J.
        • Becker K.L.
        • Kite P.
        • et al.
        Calcitonin precursors: early markers of gut barrier dysfunction in patients with acute pancreatitis.
        Pancreas. 2003; 27: 239-243
        • Yaegashi Y.
        • Endo S.
        • Inada H.T.
        • et al.
        Soluble CD14 subtype as a new diagnostic marker of sepsis.
        Shock. 2004; 21: 108
        • Wright S.D.
        • Ramos R.A.
        • Tobias P.S.
        • et al.
        CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein.
        Science. 1990; 249: 1431-1433
        • Shirakawa K.
        • Naitou K.
        • Takeuchi T.
        • et al.
        Fast detection of sepsis by new biomaker, soluble CD14 subtype.
        Crit Care Med. 2006; 34: A103
        • Saito J.
        • Hashiba E.
        • Mikami A.
        • et al.
        Pilot study of changes in presepsin concentrations compared with changes in procalcitonin and C-reactive protein concentrations after cardiovascular surgery.
        J Cardiothorac Vasc Anesth. 2017; 31: 1262-1267
        • Koh H.
        • Aimoto M.
        • Katayama T.
        • et al.
        Diagnostic value of levels of presepsin (soluble CD14-subtype) in febrile neutropenia in patients with hematological disorders.
        J Infect Chemother. 2016; 22: 466-471
        • Endo S.
        • Suzuki Y.
        • Takahashi G.
        • et al.
        Usefulness of presepsin in the diagnosis of sepsis in a multicenter prospective study.
        J Infect Chemother. 2012; 18: 891-897
        • Rittirsch D.
        • Huber-Lang M.S.
        • Flierl M.A.
        • et al.
        Immunodesign of experimental sepsis by cecal ligation and puncture.
        Nat Protoc. 2009; 4: 31-36
        • Chaudry I.H.
        • Wichterman K.A.
        • Baue A.E.
        Effect of sepsis on tissue adenine nucleotide levels.
        Surgery. 1979; 85: 205-211
        • Hotchkiss C.E.
        • Merritt A.M.
        Evaluation of cecal ligation as a model of mucoid enteropathy in specific-pathogen-free rabbits.
        Lab Anim Sci. 1996; 46: 174-178
        • Yamamoto K.
        • Loskutoff D.J.
        Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator.
        J Clin Invest. 1996; 97: 2440-2451
        • Thomas R.C.
        • Bath M.F.
        • Stover C.M.
        • et al.
        Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system.
        Peptides. 2014; 61: 56-60
        • Hamesch K.
        • Borkham-Kamphorst E.
        • Strnad P.
        • et al.
        Lipopolysaccharide-induced inflammatory liver injury in mice.
        Lab Anim. 2015; 49: 37-46
        • Hys M.
        • Rutyna R.
        • Psujek O.
        • et al.
        High serum procalcitonin concentration and dynamics of its changes as a prognostic factor of mortality.
        Anaesthesiol Intensive Ther. 2018; 50: 88-89
        • Assicot M.
        • Gendrel D.
        • Carsin H.
        • et al.
        High serum procalcitonin concentrations in patients with sepsis and infection.
        Lancet. 1993; 341: 515-518
        • Li J.L.
        • Li G.
        • Jing X.Z.
        • et al.
        Assessment of clinical sepsis-associated biomarkers in a septic mouse model.
        J Int Med Res. 2018; 46: 2410-2422
        • Wang J.
        • Zhou J.
        • Bai S.
        Combination of glutamine and ulinastatin treatments greatly improves sepsis outcomes.
        J Inflamm Res. 2020; 13: 109-115
        • Efstathiou S.P.
        • Pefanis A.V.
        • Tsiakou A.G.
        • et al.
        Fever of unknown origin: discrimination between infectious and non-infectious causes.
        Eur J Intern Med. 2010; 21: 137-143
        • Shimazaki S.
        • Mishima S.
        Experimental animal model of sepsis and septic shock.
        JJAAM. 1994; 5: 1-14
        • Pettilä V.
        • Hynninen M.
        • Takkunen O.
        • et al.
        Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis.
        Intensive Care Med. 2002; 28: 1220-1225
        • Seymour C.W.
        • Gesten F.
        • Prescott H.C.
        • et al.
        Time to treatment and mortality during mandated emergency care for sepsis.
        N Engl J. 2017; 23: 2235-2244
        • Nakamura Y.
        • Hoshino K.
        • Kiyomi F.
        • et al.
        Comparison of accuracy of presepsin and procalcitonin concentrations in diagnosing sepsis in patients with and without acute kidney injury.
        Clin Chim Acta. 2019; 490: 200-206
        • Takeuchi M.
        • Yokose T.
        • Kawakubo H.
        • et al.
        The perioperative presepsin as an accurate diagnostic marker of postoperative infectious complications after esophagectomy: a prospective cohort study.
        Esophagus. 2020; 17: 399-407
        • Yokose T.
        • Takeuchi M.
        • Obara H.
        • et al.
        Diagnostic utility of Presepsin in infections after liver transplantation: a preliminary study.
        Ann Transpl. 2021; 26: e933774-e933774-12
        • Diodato M.D.
        • Knoferl M.W.
        • Schwacha M.G.
        • et al.
        Gender differences in the inflammatory response and survival following hemorrhage and subsequent sepsis.
        Cytokine. 2001; 14: 162-169
        • Li P.
        • Allen H.
        • Banerjee S.
        • Franklin S.
        • et al.
        Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock.
        Cell. 1995; 80: 401-411
        • Nishida O.
        • Ogura H.
        • Egi M.
        • et al.
        The Japanese clinical practice guidelines for management of sepsis and septic shock (J-SSCG) 2016.
        J Intensive Care. 2018; 5: 3-89
        • Lei W.
        • Qiao L.
        • Anqi L.
        • et al.
        Puerarin increases survival and protects against organ injury by suppressing NF-κB/JNK signaling in experimental sepsis.
        Front Pharmacol. 2020; 11560
        • Junyan W.
        • Jiahui Z.
        • Shuancheng B.
        Combination of glutamine and ulinastin treatments greatly improves sepsis outcomes.
        J Inflamm Res. 2020; 13: 105-109