Kazan medical journalKazan medical journal0368-48142587-9359Eco-Vector200310.17816/KMJ2003Research ArticleThe clinical significance of acute phase proteins as inflammatory markers in infectious diseasesDudinaK Rdudinakr@mail.ruKutateladzeM M-ZnoikoO O-BokovaN O-ShutkoS A-FilinaL D-OgarevV V-YushchukN D-Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Moscow, Russia1512201495690991528032016Copyright © 2014, Dudina K.R., Kutateladze M.M., Znoiko O.O., Bokova N.O., Shutko S.A., Filina L.D., Ogarev V.V., Yushchuk N.D.2014The article reviews the clinical significance of measuring acute phase proteins (procalcitonin, C-reactive protein and neopterin) for differential diagnosis between bacterial and viral infections. The results of researches preformed at 1984 to 2014, which measured the levels of C-reactive protein, procalcitonin and neopterin in body biological fluids in infectious and non-infection diseases, are analyzed. Most frequently the clinician encounters a situation when it is necessary to differentiate the bacterial infection from other possible causes of increased body temperature, in particular, from viral infections. In some cases, the diagnosis of bacterial infection is possible only after the results of bacteriology, therefore, laboratory markers of bacterial infection, which would allow differentiating the causes of fever and minimizing the number of cases of unjustified antibiotic use, are actively sought out. Combined measuring of three acute inflammation markers was performed in patients with both infectious and non- infectious diseases. In was revealed that the levels of those blood markers correlate with the inflammation severity. Higher diagnostic value of simultaneous measurement of C-reactive protein, procalcitonin and neopterin, as well as the predictive value of procalcitonin and neopterin in monitoring the course of a number of diseases, was shown. Comprehensive analysis of the concentrations of the studied biomarkers in relation to clinical and microbiological data may help to identify patients at high risk of an unfavorable course of some diseases, allowing timely administration of all necessary treatments.procalcitoninC-reactive proteinneopterininfectious diseasesacute phase proteinsпрокальцитонинС-реактивный белокнеоптерининфекционные заболеваниямаркёры острого воспаления[Дегтярёва О.В., Петюнина О.В. Сывороточный неоптерин и С-реактивный белок у больных с разными клиническими вариантами острого коронарного синдрома // Украин. терап. ж. - 2008. - №1. - С. 41-44.][Королёва О.С., Затейщиков Д.А. Биомаркёры в кардиологии: регистрация внутрисосудистого воспаления // Фарматека. - 2007. - №8. - С. 30-36.][Назаров П.Г. Реактанты острой фазы воспаления. - СПб: Наука, 2001. - 423 с.][Потемина Т.Е., Ляляев В.А., Кузнецова С.В. Системные изменения в организме при воспалении. Хроническое воспаление. - Н. Новгород: изд-во НижГМА, 2010. - 33 с.][Симбирцев А.С. Цитокины: классификация и биологические функции // Цитокины и воспаление. - 2004. - №3 (2). - С. 16-21.][Akbulut H.H., Celik I., Akbulut A. et al. Serum neopterin levels in patients with brucellosis // J. Infect. - 2005. - Vol. 51, N 4. - P. 281-286.][Assicot M., Gendrel D., Carsin H. et al. High serum procalcitonin concentrations in patients with sepsis and infection // Lancet. - 1993. - Vol. 341, N 8844. - P. 515-518.][Balázs C., Türke B., Vámos A. Determination of serum neopterin levels in patients with autoimmune thyroid diseases // Orv. Hetil. - 2012. - Vol. 153, N 29. - P. 1127-1131.][Barutcuoglu B., Bozdemir A.E., Dereli D. et al. Increased serum neopterin levels in women with polycystic ovary syndrome // Ann. Clin. Lab. Sci. - 2006. - Vol. 36, N 3. - P. 267-272.][Baydar T., Yuksel O., Sahin T.T. et al. Neopterin as a prognostic biomarker in intensive care unit patients // J. Crit. Care. - 2009. - Vol. 24, N 3. - P. 318-321.][Bertram L., Liss Y., Grözinger M. Neopterin and C-reactive protein in the course of Stevens-Johnson syndrome: report of a case // Acta. Derm. Venereol. - 2009. - Vol. 89, N 3. - P. 285-287.][Bipath P., Viljoen M, Levay P.F. Levels of procalcitonin, C-reactive protein and neopterin in patients with advanced HIV-1 infection // SAJHIVMED. - 2012. - Vol. 13, N 2. - P. 78-82.][Brunkhorst F.M., Wegscheider K., Forycky Z.E. et al. Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock // Intensive Care Med. - 2000. - Vol. 26, N 2. - P. 148-152.][Cakan G., Bezirci F.B., Kacka A. et al. Assessment of diagnostic enzyme-linked immunosorbent assay kit and serological markers in human brucellosis // Jpn. J. Infect. Dis. - 2008. - Vol. 61, N 5. - P. 366-370.][Carpenter L.L., Gawug C.E., Tyrka A.R., Price L.H. C-reactive protein, early life stress, and wellbeing in healthy adults // Act. Psychiatr. Scand. - 2012. - Vol. 126, N 6. - P. 402-410.][Chan C.P., Choi J.W., Cao K.Y. et al. Detection of serum neopterin for early assessment of dengue virus infection // J. Infect. - 2006. - Vol. 53, N 3. - P. 152-158.][Charles P.E., Dalle F., Aho S. et al. Serum procalcitonin measurement contribution to the early diagnosis of candidemia in critically ill patients // Intensive Care Med. - 2006. - Vol. 32, N 10. - P. 1577-1583.][Christ-Crain M., Müller B. Procalcitoninum in bacterial infections: hype, hope, more or less? // Swiss. Med. Wkly. - 2005. - Vol. 135, N 31-32. - P. 451-460.][Christofilopoulou S., Charvalos E., Petrikkos G. Could procalcitonin be a predictive biological marker in systemic fungal infections? Study of 14 cases // Eur. J. Intern. Med. - 2002. - Vol. 13, N 8. - P. 493-495.][Dornbusch H.J., Strenger V., Kerbl R. et al. Procalcitonin - a marker of invasive fungal infection? // Support Care Cancer. - 2005. - Vol. 13, N 5. - P. 343-346.][Eberhard O.K., Haubitz M., Brunkhorst F.M. et al. Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection // Arthritis Rheum. - 1997. - Vol. 40, N 7. - P. 1250-1256.][Fang H.Y., Huang X.Y., Chien H.T. et al. Refining the role of preoperative C-reactive protein by neutrophil/lymphocyte ratio in oral cavity squamous cell carcinoma // Laryngoscope. - 2013. - Vol. 123, N 11. - P. 2690-2699.][Fuchs D., Avanzas P., Arroyo-Espliguero R. et al. The role of neopterin in atherogenesis and cardiovascular risk assessment // Curr. Med. Chem. - 2009. - Vol. 16, N 35. - P. 4644-4653.][Greksova K., Parrak V., Chovancova D. et al. Procalcitonin, neopterin and C-reactive protein in diagnostics of intrauterine infection and preterm delivery // Bratisl. Lek. Listy. - 2009. - Vol. 110, N 10. - P. 623-626.][Hatzistilianou M., Rekleity A., Athanassiadou F. et al. Serial procalcitonin responses in infection of children with secondary immunodeficiency // Clin. Invest. Med. - 2007. - Vol. 30, N 2. - P. E75-85.][Ilhan F., Akbulut H., Karaca I. et al. Procalcitonin, C-reactive protein and neopterin levels in patients with coronary atherosclerosis // Acta. Cardiol. - 2005. - Vol. 60, N 4. - P. 361-365.][Ip M., Rainer T.H., Lee N. et al. Value of serum procalcitonin, neopterin, and C-reactive protein in differentiating bacterial from viral etiologies in patients presenting with lower respiratory tract infections // Diagn. Microbiol. Infect. Dis. - 2007. - Vol. 59, N 2. - P. 131-136.][Korppi M., Kroger L. C-reactive protein in viral and bacterial respiratory infection // Scand. J. Infect. Dis. - 1993. - Vol. 25, N 2. - P. 207-213.][Kremsner P.G., Winkler S., Wildling E. High plasma levels of nitrogen oxides are associated with severe disease and correlate with rapid parasitological and clinical cure in Plasmodium falciparum malaria // Trans. R. Soc. Trop. Med. Hyg. - 1996. - Vol. 90, N 1. - P. 44-47.][Kronborg C.S., Knudsen U.B., Moestrup S.K. et al. Serum markers of macrophage activation in pre-eclampsia: no predictive value of soluble CD163 and neopterin // Acta. Obstet. Gynecol. Scand. - 2007. - Vol. 86, N 9. - P. 1041-1046.][Kurz K., Garimorth K., Joannidis M. et al. Altered immune responses during septicaemia in patients suffering from haematological malignancies // Int. J. Immunopathol. Pharmacol. - 2012. - Vol. 25, N 1. - P. 147-156.][Lacoma A., Bas A., Tudela P. et al. Correlation of inflammatory and cardiovascular biomarkers with pneumonia severity scores // Enferm. Infecc. Microbiol. Clin. - 2014. - Vol. 32, N 3. - P. 140-146.][Lacoma A., Prat C., Andreo F. et al. Value of procalcitonin, C-reactive protein, and neopterin in exacerbations of chronic obstructive pulmonary disease // Int. J. Chron. Obstruct. Pulmon. Dis. - 2011. - Vol. 6. - P. 157-169.][Lee J.Y., Hwang S.J., Shim J.W. et al. Clinical significance of serum procalcitonin in patients with community-acquired lobar pneumonia // Korean J. Lab. Med. - 2010. - Vol. 30, N 4. P. 406-413.][Łuczak G., Plata-Nazar K, Kozielska E. et al. Serum neopterin level in children with lower respiratory tract infections // Med. Wieku. Rozwoj. - 2007. - Vol. 11, N 4. - P. 423-427.][Meisner M., Tschaikowsky K., Hutzler A. et al. Postoperative plasma concentrations of procalcitonin after different types of surgery // Intensive Care Med. - 1998. - Vol. 24, N 7. - P. 680-684.][Mesquida M., Molins B., Llorenç V.I. et al. Proinflammatory cytokines and C-reactive protein in uveitis associated with Behçet’s disease // Mediators Inflamm. - 2014. - doi: 10.1155/2014/396204. - Epub. 2014 Jun. 8.][Müller F., Christ-Crain M., Bregenzer T. et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial // Chest. - 2010. - Vol. 138, N 1. - P. 121-129.][Musunuru K., Kral B.G., Blumenthal R.S. et al. The use of high sensitivity C-reactive protein in clinical practice // Nat. Clin. Pract. Cardiovasc. Med. - 2008. - Vol. 5, N 10. - P. 621-635.][O’Grady N.P., Barie P.S., Bartlett J.G. et al. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America // Crit. Care Med. - 2008. - Vol. 36, N 4. - P. 1330-1349.][Oleszczuk J., Wawrzycka B., Maj J.G. Interleukin-6 and neopterin levels in serum of patients with preterm labour with and without infection // Eur. J. Obstet. Gynecol. Reprod. Biol. - 1997. - Vol. 74, N 1. - P. 27-30.][Pearson T.A., Mensah G.A., Alexander R.W. et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and American Heart Association // Circulation. - 2003. - Vol. 107. - P. 499-551.][Picariello C., Lazzeri C., Valente S. et al. Procalcitonin in acute cardiac patients // Intern. Emerg. Med. - 2011. - Vol. 6. - P. 245-252.][Pourakbari B., Mamishi S., Zafari J. et al. Evaluation of procalcitonin and neopterin level in serum of patients with acute bacterial infection // Braz. J. Infect. Dis. - 2010. - Vol. 14, N 3. - P. 252-255.][Prat C., Domínguez J., Andreo F. et al. Procalcitonin and neopterin correlation with aetiology and severity of pneumonia // J. Infect. - 2006. - Vol. 52, N 3. - P. 169-177.][Prat C., Sancho J.M., Dominguez J. et al. Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia // Leuk. Lymphoma. - 2008. - Vol. 49, N 9. - P. 1752-1761.][Rainer T.H., Chan C.P., Leung M.F. et al. Diagnostic utility of CRP to neopterin ratio in patients with acute respiratory tract infections // J. Infect. - 2009. - Vol. 58, N 2. - P. 123-130.][Redl H., Schlag G., Tögel E. et al. Procalcitonin release patterns in a baboon model of trauma and sepsis: relationship to cytokines and neopterin // Crit. Care Med. - 2000. - Vol. 28, N 11. - P. 3659-3663.][Reibnegger G., Fuchs D., Grubauer G. et al. Neopterin excretion during incubation period, clinical manifestation and reconvalescence of viral infection // Biochem. Clin. Asp. Pteridines. - 1984. - Vol. 3. - P. 433-447.][Reinhart K., Bauer M., Riedelmann N.C., Hartog C.S. New approaches to sepsis: molecular diagnostics and biomarkers // Clin. Microbiol. Rev. - 2012. - Vol. 25. - P. 609-634.][Reinhart K., Meisner M., Brunkhorst F.M. Markers for sepsis diagnosis: what is useful? // Crit. Care Clin. - 2006. - Vol. 22. - P. 503-519.][Ruokonen E., Ilkka L., Niskanen M., Takala J. Procalcitonin and neopterin as indicators of infection in critically ill patients // Acta. Anaesthesiol. Scand. - 2002. - Vol. 46, N 4. - P. 398-404.][Ruokonen E., Nousiainen T., Pulkki K., Takala J. Procalcitonin concentrations in patients with neutropenic fever // Eur. J. Clin. Microbiol. Infect. Dis. - 1999. - Vol. 18, N 4. - P. 283-285.][Sponholz C., Sakr Y., Reinhart K., Brunkhorst F. Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature // Crit. Care. - 2006. - Vol. 10, N 5. - P. R145.][Tasdelen F.N., Aliyazicioglu Y., Tanyel E. et al. The value of neopterin and procalcitonin in patients with sepsis // South Med. J. - 2010. - Vol. 103, N 3. - P. 216-219.][Van Haelst P.L., van Doormaal J.J., May J.F. et al. Secondary prevention with fluvastatin decreases levels of adhesion molecules, neopterin and C-reactive protein // Eur. J. Intern. Med. - 2001. - Vol. 12, N 6. - P. 503-519.][Van Nieuwkoop C., Bonten T.N., van’t Wout J.W. et al. Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study // Crit. Care. - 2010. - Vol. 14, N 6. - P. R206.][Vedrine C., Caraion C., Lambert C., Genin C. Cytometric bead assay of cytokines in sepsis: a clinical evaluation // Cytometry B. Clin. Cytom. - 2004. - Vol. 60, N 1. - P. 14-22.][Whicher J., Bienvenu J., Monneret G. Procalcitonin as an acute phase marker // Ann. Clin. Biochem. - 2001. - Vol. 38, Pt. 5. - P. 483-493.][Zheng B., Cao K.Y., Chan C.P. et al. Serum neopterin for early assessment of severity of severe acute respiratory syndrome // Clin. Immunol. - 2005. - Vol. 116, N 1. - P. 18-26.]