Abstract
C-reactive protein (CRP) is an acute-phase protein that is produced in large amounts by hepatocytes, upon stimulation by the cytokines interleukin-6, tumor-necrosis-factor-α and interleukin-1β, during an acute-phase response. CRP is an objective marker of inflammation and, in gastrointestinal diseases such as Crohn's disease and acute pancreatitis, its levels correlate well with clinical disease activity. In contrast to its use as a marker in Crohn's disease, however, CRP is a less reliable marker of inflammation and disease activity in patients with ulcerative colitis, except perhaps for severe, extensive colitis. The increased production of CRP after an acute-phase stimulus, such as active gut inflammation, might explain why strong anti-inflammatory agents, such as anti-tumor-necrosis-factor-α antibodies and other biologic agents, work particularly well in patients with increased levels of CRP. CRP is also useful as a laboratory marker to predict prognosis and relapse in patients with Crohn's disease and acute pancreatitis. Elevated CRP levels have been associated with an increased risk of colorectal cancer and are a marker of poor prognosis, indicating more advanced disease and, possibly, reduced survival. An important question that remains is how often CRP levels should be measured. Until there are more data, the use of CRP and of other biomarkers should be seen as an additional tool that aids clinical observation and physical examination, but that cannot replace it.
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References
Tall AR (2004) C-reactive protein reassessed. N Engl J Med 350: 1450–1452
Pepys MB et al. (1977) Immunological studies in inflammatory bowel disease. In: Immunology of the Gut, Ciba Foundation Symposium 283–297 (Eds Porter R and Knight J). Amsterdam: Elsevier/Excerpta Medica
Vigushin DM et al. (1993) Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest 91: 1351–1357
Saverymuttu SH et al. (1986) Differing acute phase responses in Crohn's disease and ulcerative colitis. Gut 27: 809–813
Rogler G (2004) Update in inflammatory bowel disease pathogenesis. Curr Opin Gastroenterol 20: 311–317
Gross V et al. (1992) Evidence for continuous stimulation of interleukin-6 production in Crohn's disease. Gastroenterology 102: 514–519
Shine B et al. (1985) C-reactive protein as an aid in the differentiation of functional and inflammatory bowel disorders. Clin Chim Acta 148: 105–109
Beattie RM et al. (1995) Indications for investigation of chronic gastrointestinal symptoms. Arch Dis Child 73: 354–355
Poullis AP et al. (2002) A new, highly sensitive assay for C-reactive protein can aid the differentiation of inflammatory bowel disorders from constipation- and diarrhoea-predominant functional bowel disorders. Eur J Gastroenterol Hepatol 14: 409–412
Fagan EA et al. (1982) Serum levels of C-reactive protein in Crohn's disease and ulcerative colitis. Eur J Clin Invest 12: 351–359
Andre C et al. (1981) Assessment of appropriate laboratory measurements to supplement the Crohn's disease acitivity index. Gut 22: 571–574
Tromm A et al. (1992) Evaluation of different laboratory tests and activity indices reflecting the inflammatory activity of Crohn's disease. Scand J Gastroenterol 27: 774–778
Ricci G et al. (1995) Comparison of serum total sialic acid, C-reactive protein, alpha 1-acid glycoprotein and beta 2-microglobulin in patients with non-malignant bowel diseases. Biomed Pharmacother 49: 259–262
Solem CA et al. (2005) Correlation of C-reactive protein (CRP) with clinical, radiographic, and endoscopic activity in inflammatory bowel disease (IBD). Inflamm Bowel Dis 11: 707–712
Ridker PM and Morrow DA (2003) C-reactive protein, inflammation, and coronary risk. Cardiol Clin 21: 315–325
Danesh J et al. (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350: 1387–1397
Bataille R et al. (1992) C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. Blood 80: 733–737
Boirivant M et al. (1988) The clinical significance of serum C reactive protein levels in Crohn's disease. Results of a prospective longitudinal study. J Clin Gastroenterol 10: 401–405
Consigny Y et al. (2001) Biological markers of short term relapse in Crohn's disease (CD) [Abstract]. Gastroenterology 20 (Suppl): A53
Brignola C et al. (1986) A laboratory index for predicting relapse in asymptomatic patients with Crohn's disease. Gastroenterology 91: 1490–1494
Travis SP et al. (1996) Predicting outcome in severe ulcerative colitis. Gut 38: 905–910
Targan SR et al. (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med 337: 1029–1035
Present DH et al. (1999) Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 340: 1398–1405
Hanauer SB et al. (2002) Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 359: 1541–1549
Sands BE et al. (2004) Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 350: 876–885
Louis E et al. (2002) A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism. Scand J Gastroenterol 37: 818–824
Sandborn WJ et al. (2004) CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn's disease: a randomised, double blind, placebo controlled trial. Gut 53: 1485–1493
Schreiber S et al. (2003) Safety of CDP870, a pegylated humanized anti-TNF antibody fragment in Crohn's disease [Abstract]. Gut 52 (Suppl): A215
Rutgeerts P et al. (2003) Subanalysis from a phase 3 study on the evaluation of natalizumab in active Crohn's disease [Abstract]. Gut 52 (Suppl): A239
Dervenis C et al. (1999) Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini consensus conference. Int J Pancreatol 25: 195–210
Wilson C et al. (1989) C-reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis. Br J Surg 76: 177–181
Viedma JA et al. (1992) Role of interleukin-6 in acute pancreatitis. Comparison with C-reactive protein and phospholipase A. Gut 33: 1264–1267
Buchler M et al. (1986) Sensitivity of antiproteases, complement factors and C-reactive protein in detecting pancreatic necrosis. Results of a prospective clinical study. Int J Pancreatol 1: 227–235
Werner J et al. (2003) Useful markers for predicting severity and monitoring progression of acute pancreatitis. Pancreatology 3: 115–127
Puolakkainen P et al. (1987) C -reactive protein (CRP) and serum phospholipase A2 in the assessment of the severity of acute pancreatitis. Gut 28: 764–771
Windsor JA (2000) Search for prognostic markers for acute pancreatitis. Lancet 355: 1924–1925
Paajanen H et al. (1995) Serum tumour necrosis factor compared with C-reactive protein in the early assessment of severity of acute pancreatitis. Br J Surg 82: 271–273
Gross V et al. (1990) Granulocyte elastase in assessment of severity of acute pancreatitis. Comparison with acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and protease inhibitor alpha 2-macroglobulin. Dig Dis Sci 35: 97–105
Hamalainen MT et al. (2002) Do normal leukocyte count and C-reactive protein on admission to hospital exclude a life-threatening attack of acute pancreatitis? Scand J Surg 91: 353–356
Imamura T et al. (2002) Significance of measurement of high-sensitivity C-reactive protein in acute pancreatitis. J Gastroenterol 37: 935–938
Kiviniemi H et al. (1994) Acute phase response in patients with uncomplicated and complicated endoscopic retrogradic cholangiopancreaticography. HPB Surg 8: 129–131
Oezcueruemez-Porsch M et al. (1998) Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis. Dig Dis Sci 43: 1763–1769
Kaw M and Singh S (2001) Serum lipase, C-reactive protein, and interleukin-6 levels in ERCP-induced pancreatitis. Gastrointest Endosc 54: 435–440
Baron JA et al. (2003) A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 348: 891–899
Giardiello FM et al. (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328: 1313–1316
Steinbach G et al. (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342: 1946–1952
Erlinger TP et al. (2004) C-reactive protein and the risk of incident colorectal cancer. JAMA 291: 585–590
Zhang SM et al. (2005) C-reactive protein levels are not associated with increased risk for colorectal cancer in women. Ann Intern Med 142: 425–432
Nozoe T et al. (1998) Significance of preoperative elevation of serum C-reactive protein as an indicator for prognosis in colorectal cancer. Am J Surg 176: 335–338
Chung YC and Chang YF (2003) Serum C-reactive protein correlates with survival in colorectal cancer patients but is not an independent prognostic indicator. Eur J Gastroenterol Hepatol 15: 369–373
McMillan DC et al. (2003) Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg 90: 215–219
Nikiteas NI et al. (2005) Serum IL-6, TNF alpha and CRP levels in Greek colorectal cancer patients: prognostic implications. World J Gastroenterol 11: 1639–1643
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Vermeire, S., Van Assche, G. & Rutgeerts, P. The role of C-reactive protein as an inflammatory marker in gastrointestinal diseases. Nat Rev Gastroenterol Hepatol 2, 580–586 (2005). https://doi.org/10.1038/ncpgasthep0359
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DOI: https://doi.org/10.1038/ncpgasthep0359
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