Markers of Collagen Synthesis and Degradation Are Increased in Serum in Severe Sepsis: a Longitudinal Study of 44 Patients

Overview

Journal Crit Care

Specialty Critical Care

Date 2009 Apr 11

PMID 19358720

Citations 19

Authors

Fiia Gaddnas

Marjo Koskela

Vesa Koivukangas

Juha Risteli

Aarne Oikarinen

Jouko Laurila

Juha Saarnio

Tero Ala-Kokko

Affiliations

Soon will be listed here.

Abstract

Introduction: Sepsis-related multiple organ dysfunction is a common cause of death in the intensive care unit. The effect of sepsis on markers of tissue repair is only partly understood. The aim of this study was to measure markers of collagen synthesis and degradation during sepsis and investigate the association with disease severity and outcome.

Methods: Forty-four patients with severe sepsis participated in the study and 15 volunteers acted as controls. Blood samples were collected for 10 days after the first sepsis-induced organ dysfunction and after three and six months. Procollagen type I and III aminoterminal propeptides (PINP and PIIINP) and cross-linked telopeptides of type I collagen (ICTP) were measured.

Results: The PIIINP concentration was elevated in the septic patients (8.8 microg/L, 25th to 75th percentile = 6.8 to 26.0) when compared with controls (3.0 microg/L, 25th to 75th percentile = 2.7 to 3.3; P < 0.001) on day one. Maximum serum PIIINP concentrations during sepsis were higher in non-survivors compared with survivors (26.1 microg/L, 25th to 75th percentile = 18.7 to 84.3; vs. 15.1 microg/L, 25th to 75th percentile = 9.6 to 25.5; P = 0.033) and in multiple organ failure (MOF) compared with multiple organ dysfunction syndrome (MODS) (24.2 ug/L, 25th to 75th percentile = 13.4 to 48.2; vs. 8.9 microg/L, 25th to 75th percentile = 7.4 to 19.4; P = 0.002). Although the PINP values of the septic patients remained within the laboratory reference values, patients with MOF had higher values than patients with MODS (79.8, 25th to 75th percentile = 44.1 to 150.0; vs.40.4, 25th to 75th percentile = 23.6 to 99.3; P = 0.007). Day one ICTP levels were elevated in septic patients compared with the controls (19.4 microg/L, 25th to 75th percentile = 12.0 to 29.8; vs. 4.1 microg/L, 25th to 75th percentile = 3.4 to 5.0; P < 0.001).

Conclusions: Markers of collagen metabolism are increased in patients with severe sepsis and can be investigated further as markers of disease severity and outcome.

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References

Borensztajn K, Stiekema J, Nijmeijer S, Reitsma P, Peppelenbosch M, Spek C . Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation. Am J Pathol. 2008; 172(2):309-20. PMC: 2312363. DOI: 10.2353/ajpath.2008.070347. View

Levy M, Fink M, Marshall J, Abraham E, Angus D, Cook D . 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003; 31(4):1250-6. DOI: 10.1097/01.CCM.0000050454.01978.3B. View

Meduri G, Tolley E, Chinn A, Stentz F, Postlethwaite A . Procollagen types I and III aminoterminal propeptide levels during acute respiratory distress syndrome and in response to methylprednisolone treatment. Am J Respir Crit Care Med. 1998; 158(5 Pt 1):1432-41. DOI: 10.1164/ajrccm.158.5.9801107. View

Jensen L, Blaehr H, Andersen C, Risteli J, Lorenzen I . Metabolism of the aminoterminal propeptide of type III procollagen in cultures of human proximal tubular cells. Scand J Clin Lab Invest. 1992; 52(1):1-8. DOI: 10.3109/00365519209085434. View

Kanangat S, Postlethwaite A, Hasty K, Kang A, Smeltzer M, Appling W . Induction of multiple matrix metalloproteinases in human dermal and synovial fibroblasts by Staphylococcus aureus: implications in the pathogenesis of septic arthritis and other soft tissue infections. Arthritis Res Ther. 2006; 8(6):R176. PMC: 1794521. DOI: 10.1186/ar2086. View

Ohyama K, Seyer J, Raghow R, Kang A . A factor from damaged rat kidney stimulates collagen biosynthesis by mesangial cells. Biochim Biophys Acta. 1990; 1053(2-3):173-8. DOI: 10.1016/0167-4889(90)90010-b. View

Weber K . Fibrosis, a common pathway to organ failure: angiotensin II and tissue repair. Semin Nephrol. 1997; 17(5):467-91. View

Thiel M, Chouker A, Ohta A, Jackson E, Caldwell C, Smith P . Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury. PLoS Biol. 2005; 3(6):e174. PMC: 1088279. DOI: 10.1371/journal.pbio.0030174. View

Budinger G, Chandel N, Donnelly H, Eisenbart J, Oberoi M, Jain M . Active transforming growth factor-beta1 activates the procollagen I promoter in patients with acute lung injury. Intensive Care Med. 2004; 31(1):121-8. PMC: 7095267. DOI: 10.1007/s00134-004-2503-2. View

10.

Dellinger R, Carlet J, Masur H, Gerlach H, Calandra T, Cohen J . Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004; 32(3):858-73. DOI: 10.1097/01.ccm.0000117317.18092.e4. View

11.

Keller F, Rehbein C, Schwarz A, Fleck M, Hayasaka A, Schuppan D . Increased procollagen III production in patients with kidney disease. Nephron. 1988; 50(4):332-7. DOI: 10.1159/000185198. View

12.

Haukipuro K, Risteli L, Kairaluoma M, Risteli J . Aminoterminal propeptide of type III procollagen in healing wound in humans. Ann Surg. 1987; 206(6):752-6. PMC: 1493338. DOI: 10.1097/00000658-198712000-00011. View

13.

Oikarinen A, Autio P, Vuori J, Vaananen K, Risteli L, Kiistala U . Systemic glucocorticoid treatment decreases serum concentrations of carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type III procollagen. Br J Dermatol. 1992; 126(2):172-8. DOI: 10.1111/j.1365-2133.1992.tb07816.x. View

14.

Thornton S, Por S, Walsh B, Penny R, Breit S . Interaction of immune and connective tissue cells: I. The effect of lymphokines and monokines on fibroblast growth. J Leukoc Biol. 1990; 47(4):312-20. DOI: 10.1002/jlb.47.4.312. View

15.

Clark J, Milberg J, Steinberg K, Hudson L . Type III procollagen peptide in the adult respiratory distress syndrome. Association of increased peptide levels in bronchoalveolar lavage fluid with increased risk for death. Ann Intern Med. 1995; 122(1):17-23. DOI: 10.7326/0003-4819-122-1-199501010-00003. View

16.

Sener G, Sehirli O, Cetinel S, Ercan F, Yuksel M, Gedik N . Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast. Prostaglandins Leukot Essent Fatty Acids. 2005; 73(6):453-62. DOI: 10.1016/j.plefa.2005.07.008. View

17.

Maish 3rd G, Shumate M, Ehrlich H, Cooney R . Tumor necrosis factor binding protein improves incisional wound healing in sepsis. J Surg Res. 1998; 78(2):108-17. DOI: 10.1006/jsre.1998.5315. View

18.

Haukipuro K, Risteli L, Kairaluoma M, Risteli J . Aminoterminal propeptide of type III procollagen in serum during wound healing in human beings. Surgery. 1990; 107(4):381-8. View

19.

Chambers R, Dabbagh K, McAnulty R, Gray A, Laurent G . Thrombin stimulates fibroblast procollagen production via proteolytic activation of protease-activated receptor 1. Biochem J. 1998; 333 ( Pt 1):121-7. PMC: 1219564. DOI: 10.1042/bj3330121. View

20.

Jensen L, Horslev-Petersen K, Toft P, Bentsen K, Grande P, SIMONSEN E . Serum aminoterminal type III procollagen peptide reflects repair after acute myocardial infarction. Circulation. 1990; 81(1):52-7. DOI: 10.1161/01.cir.81.1.52. View