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01.12.2008 | Original

Serum levels of osteopontin are increased in SIRS and sepsis

verfasst von: Rosanna Vaschetto, Stefania Nicola, Carlo Olivieri, Elena Boggio, Fabio Piccolella, Riccardo Mesturini, Federica Damnotti, Davide Colombo, Paolo Navalesi, Francesco Della Corte, Umberto Dianzani, Annalisa Chiocchetti

Erschienen in: Intensive Care Medicine | Ausgabe 12/2008

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Abstract

Objective

In sepsis, dysregulation of the immune response leads to rapid multiorgan failure and death. Accurate and timely diagnosis is lifesaving and should discriminate sepsis from the systemic inflammatory response syndrome (SIRS) caused by non-infectious agents. Osteopontin acts as an extracellular matrix component or a soluble cytokine in inflamed tissues. Its exact role in immune response and sepsis remains to be elucidated. Therefore, we investigated the role of osteopontin in SIRS and sepsis.

Design

Prospective, observational study.

Setting

Intensive care unit of a university hospital.

Patients and participants

Fifty-six patients with SIRS or sepsis and 56 healthy subjects were enrolled.

Interventions

We analyzed the serum levels of osteopontin and TH1–TH2 cytokines and investigated the role of osteopontin on interleukin 6 secretion by monocytes.

Measurements and main results

Serum osteopontin levels were strikingly higher in patients than in controls and in sepsis than in SIRS, and decreased during the resolution of both the disorders. Receiver operating characteristic curves showed that osteopontin levels have discriminative power between SIRS and sepsis with an area under the curve of 0.796. Osteopontin levels directly correlated with those of interleukin 6 and in vitro, recombinant osteopontin increased interleukin 6 secretion by monocytes in both the absence and presence of high doses of lipopolysaccharide.

Conclusion

These data suggest that osteopontin might be a mediator involved in the pathogenesis of SIRS and sepsis, possibly by supporting interleukin 6 secretion.

Descriptor

45. SIRS/Sepsis: clinical studies.

Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, Sicignano A, Palazzo M, Moreno R, Boulme R, Lepage E, Le GR (2002) Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med 28:108–121PubMedCrossRef

Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD (1998) The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 244:379–386PubMedCrossRef

Cohen J, Carlet J (1996) INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med 24:1431–1440PubMedCrossRef

Fisher CJ Jr, Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL et al (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA 271:1836–1843PubMedCrossRef

Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, Rittling SR, Denhardt DT, Glimcher MJ, Cantor H (2000) Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287:860–864PubMedCrossRef

Gravallese EM (2003) Osteopontin: a bridge between bone and the immune system. J Clin Invest 112:147–149PubMed

Rollo EE, Laskin DL, Denhardt DT (1996) Osteopontin inhibits nitric oxide production and cytotoxicity by activated RAW264.7 macrophages. J Leukoc Biol 60:397–404PubMed

Takahashi F, Takahashi K, Shimizu K, Cui R, Tada N, Takahashi H, Soma S, Yoshioka M, Fukuchi Y (2004) Osteopontin is strongly expressed by alveolar macrophages in the lungs of acute respiratory distress syndrome. Lung 182:173–185PubMed

Mishima R, Takeshima F, Sawai T, Ohba K, Ohnita K, Isomoto H, Omagari K, Mizuta Y, Ozono Y, Kohno S (2007) High plasma osteopontin levels in patients with inflammatory bowel disease. J Clin Gastroenterol 41:167–172PubMedCrossRef

10.

Wong CK, Lit LC, Tam LS, Li EK, Lam CW (2005) Elevation of plasma osteopontin concentration is correlated with disease activity in patients with systemic lupus erythematosus. Rheumatology (Oxford) 44:602–606CrossRef

11.

Chiocchetti A, Comi C, Indelicato M, Castelli L, Mesturini R, Bensi T, Mazzarino MC, Giordano M, D’Alfonso S, Momigliano-Richiardi P, Liguori M, Zorzon M, Amoroso A, Trojano M, Monaco F, Leone M, Magnani C, Dianzani U (2005) Osteopontin gene haplotypes correlate with multiple sclerosis development and progression. J Neuroimmunol 163:172–178PubMedCrossRef

12.

Vogt MH, Lopatinskaya L, Smits M, Polman CH, Nagelkerken L (2003) Elevated osteopontin levels in active relapsing-remitting multiple sclerosis. Ann Neurol 53:819–822PubMedCrossRef

13.

Inomata S, Shijubo N, Kon S, Maeda M, Yamada G, Sato N, Abe S, Uede T (2005) Circulating interleukin 18 and osteopontin are useful to evaluate disease activity in patients with tuberculosis. Cytokine 30:203–211PubMedCrossRef

14.

Arai M, Yokosuka O, Kanda T, Fukai K, Imazeki F, Muramatsu M, Seki N, Miyazaki M, Ochiai T, Hirasawa H, Saisho H (2006) Serum osteopontin levels in patients with acute liver dysfunction. Scand J Gastroenterol 41:102–110PubMedCrossRef

15.

American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874

16.

Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMedCrossRef

17.

Vincent JL, Moreno R, Takala J, Willatts S, de MA, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710

18.

Metz CE, Herman BA, Shen JH (1998) Maximum likelihood estimation of receiver operating characteristic (ROC) curves from continuously-distributed data. Stat Med 17:1033–1053PubMedCrossRef

19.

Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, Vadas L, Pugin J (2001) Diagnostic value of procalcitonin, interleukin 6, and interleukin 8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 164:396–402PubMed

20.

Oberholzer A, Souza SM, Tschoeke SK, Oberholzer C, Abouhamze A, Pribble JP, Moldawer LL (2005) Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis. Shock 23:488–493PubMed

21.

Jain S, Chakraborty G, Bulbule A, Kaur R, Kundu GC (2007) Osteopontin: an emerging therapeutic target for anticancer therapy. Expert Opin Ther Targets 11:81–90PubMedCrossRef

22.

Jansson M, Panoutsakopoulou V, Baker J, Klein L, Cantor H (2002) Cutting edge: attenuated experimental autoimmune encephalomyelitis in eta-1/osteopontin-deficient mice. J Immunol 168:2096–2099PubMed

23.

O’Regan AW, Nau GJ, Chupp GL, Berman JS (2000) Osteopontin (Eta-1) in cell-mediated immunity: teaching an old dog new tricks. Immunol Today 21:475–478PubMedCrossRef

24.

Comabella M, Pericot I, Goertsches R, Nos C, Castillo M, Blas NJ, Rio J, Montalban X (2005) Plasma osteopontin levels in multiple sclerosis. J Neuroimmunol 158:231–239PubMedCrossRef

25.

Nau GJ, Chupp GL, Emile JF, Jouanguy E, Berman JS, Casanova JL, Young RA (2000) Osteopontin expression correlates with clinical outcome in patients with mycobacterial infection. Am J Pathol 157:37–42PubMed

26.

Yamaguchi H, Igarashi M, Hirata A, Tsuchiya H, Sugiyama K, Morita Y, Jimbu Y, Ohnuma H, Daimon M, Tominaga M, Kato T (2004) Progression of diabetic nephropathy enhances the plasma osteopontin level in type 2 diabetic patients. Endocr J 51:499–504PubMedCrossRef

27.

Zhao L, Li T, Wang Y, Pan Y, Ning H, Hui X, Xie H, Wang J, Han Y, Liu Z, Fan D (2008) Elevated plasma osteopontin level is predictive of cirrhosis in patients with hepatitis B infection. Int J Clin Pract 62(7):1056–1062

28.

D’Alfonso S, Barizzone N, Giordano M, Chiocchetti A, Magnani C, Castelli L, Indelicato M, Giacopelli F, Marchini M, Scorza R, Danieli MG, Cappelli M, Migliaresi S, Bigliardo B, Sabbadini MG, Baldissera E, Galeazzi M, Sebastiani GD, Minisola G, Ravazzolo R, Dianzani U, Momigliano-Richiardi P (2005) Two single-nucleotide polymorphisms in the 5′ and 3′ ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum 52:539–547PubMedCrossRef

29.

Tang BM, Eslick GD, Craig JC, McLean AS (2007) Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 7:210–217PubMedCrossRef

30.

Meisner M (2002) Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta 323:17–29PubMedCrossRef

31.

Giamarellos-Bourboulis EJ, Mega A, Grecka P, Scarpa N, Koratzanis G, Thomopoulos G, Giamarellou H (2002) Procalcitonin: a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient? Intensive Care Med 28:1351–1356PubMedCrossRef

32.

Ruokonen E, Ilkka L, Niskanen M, Takala J (2002) Procalcitonin and neopterin as indicators of infection in critically ill patients. Acta Anaesthesiol Scand 46:398–404PubMedCrossRef

33.

Tugrul S, Esen F, Celebi S, Ozcan PE, Akinci O, Cakar N, Telci L (2002) Reliability of procalcitonin as a severity marker in critically ill patients with inflammatory response. Anaesth Intensive Care 30:747–754PubMed

34.

Wanner GA, Keel M, Steckholzer U, Beier W, Stocker R, Ertel W (2000) Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients. Crit Care Med 28:950–957PubMedCrossRef

35.

Doellner H, Arntzen KJ, Haereid PE, Aag S, Austgulen R (1998) Interleukin 6 concentrations in neonates evaluated for sepsis. J Pediatr 132:295–299PubMedCrossRef

36.

Resch B, Gusenleitner W, Muller WD (2003) Procalcitonin and interleukin 6 in the diagnosis of early-onset sepsis of the neonate. Acta Paediatr 92:243–245PubMed

37.

Akira S, Isshiki H, Sugita T, Tanabe O, Kinoshita S, Nishio Y, Nakajima T, Hirano T, Kishimoto T (1990) A nuclear factor for IL6 expression (NF-IL6) is a member of a C/EBP family. EMBO J 9:1897–1906PubMed

38.

O’Regan AW, Hayden JM, Body S, Liaw L, Mulligan N, Goetschkes M, Berman JS (2001) Abnormal pulmonary granuloma formation in osteopontin-deficient mice. Am J Respir Crit Care Med 164:2243–2247PubMed

39.

Persy VP, Verhulst A, Ysebaert DK, De Greef KE, De Broe ME (2003) Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice. Kidney Int 63:543–553PubMedCrossRef

40.

Nau GJ, Liaw L, Chupp GL, Berman JS, Hogan BL, Young RA (1999) Attenuated host resistance against Mycobacterium bovis BCG infection in mice lacking osteopontin. Infect Immun 67:4223–4230PubMed

Titel: Serum levels of osteopontin are increased in SIRS and sepsis
verfasst von: Rosanna Vaschetto
Stefania Nicola
Carlo Olivieri
Elena Boggio
Fabio Piccolella
Riccardo Mesturini
Federica Damnotti
Davide Colombo
Paolo Navalesi
Francesco Della Corte
Umberto Dianzani
Annalisa Chiocchetti
Publikationsdatum: 01.12.2008
Verlag: Springer-Verlag
Erschienen in: Intensive Care Medicine / Ausgabe 12/2008
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-008-1268-4

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Serum levels of osteopontin are increased in SIRS and sepsis