Influence of recombinant human procalcitonin on phagocytic and candidacidal ability of polymorphonuclear leukocytes and on killing mechanisms of serum and blood against bacteria Staphylococcus aureus and Escherichia coli

Czech version

Authors: T. Pinčíková ¹; M. Bucová ¹; L. Slobodníková ²
Authors‘ workplace: Imunologický ústav Lekárskej fakulty UK, Bratislava, Slovenská republika, prednosta prof. MUDr. Milan Buc, DrSc. ¹; Mikrobiologický ústav Lekárskej fakulty UK, Bratislava, Slovenská republika, prednosta prof. MUDr. Daniela Kotulová, CSc. ²
Published in: Vnitř Lék 2005; 51(12): 1365-1370
Category: Original Contributions

Overview

Procalcitonin (PCT) is a highly selective and specific marker for early diagnosis of sepsis. There is enough information confirming that procalcitonin should be considered as an important mediator in the pathophysiology of sepsis. The aim of our work was to evaluate the effect of recombinant human procalcitonin (rhPCT) on phagocytic and candidacidal activity of polymorphonuclear leukocytes (PMNL) in blood, as well as on killing mechanisms of fresh serum and blood against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Our results show that rhPCT dose dependently decreased both phagocytic and candidacidal activity of polymorphonuclear leukocytes (p < 0.001). RhPCT inhibited also the microbicidal activity of both serum and blood on E. coli that was found by inoculation of suspension on culture plates. We found that rhPCT supported the E. coli colony count increase during the incubation in the presence of both serum and blood. The effect of rhPCT on the S. aureus colony count increase was not statistically significant. Conclusion: Our results indicate a suppressive effect of rhPCT on phagocytic and microbicidal activity of polymorphonuclear leucocytes.

Key words:
phagocytosis - immunity - microorganism - polymorphonuclear leukocytes - procalcitonin - sepsis

Sources

1. Le Moullec JM, Jullienne A, Chenais J, et al. The complete sequence of human preprocalcitonin. FEBS Lett 1984; 167: 93-97.

2. Becker KL, Müller B, Nylén ES at al. Calcitonin gene family of peptides. Structure, molecular biology and effects. In: Bilizikian JP, Raisz LG, Rodin GA (eds). Principles of Bone Biology. 2nd ed. San Diego: Academic Press 2002: 616-639.

3. Broad PM, Symes AJ, Thakker RV et al. Structure and methylation of the human calcitonin/alpha-CGRP gene. Nucleic Acids Res 1989; 17: 6999-7011.

4. Becker KL, Müller B, Nylén ES et al. Calcitonin gene family of peptides. In: Principles and Practice of Endocrinology and Metabolism. Philadelphia: J. B. Lippincott 2001: 520-534.

5. Müller B, White JC, Nylén ES et al. Ubiquitous expression of the calcitonin-1 gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab 2001; 86: 396-404.

6. Brunkhorst FM, Wegscheider K, Forycki ZF et al. Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic schock. Intens Care Med 2000; 26: 148-152.

7. Jimeno A, García-Velasco A, Del Val O et al. Assessment of procalcitonin as a diagnostic and prognostic marker in patients with solid tumors and febrile neutropenia. Cancer 2004; 100: 2462-2469.

8. Müller B, Becker KL. Procalcitonin: how a hormone became a marker and mediator of sepsis. Swiss Med Wkly 2001; 131: 595-602.

9. Balog A, Ocsovszki I, Mandi Y. Flow cytometric analysis of procalcitonin expression in human monocytes and granulocytes. Immunol Lett 2002; 84: 199-203.

10. Oberhoffer M, Stonans I, Russwurm S et al. Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro. J Lab Clin Med 1999; 134: 49-55.

11. Morgenthaler NG, Struck J, Chancerelle Y et al. Production of procalcitonin (PCT) in non-thyroidal tissue after LPS injection. Horm Metab Res 2003; 35: 290-295.

12. Becker KL, Nylén ES, Snider RH et al. Immunoneutralization of procalcitonin as therapy of sepsis. Journal of Endotoxin Research 2003; 9: 367-374.

13. Meisner M, Muller V, Khakpour Z et al. Induction of procalcitonin and proinflammatory cytokines in an anhepatic baboon endotoxin shock model. Shock 2003; 19: 187-190.

14. Maruna P, Nedelnikova K, Gürlich R. Physiology and genetics of procalcitonin. Physiol Res 2000; 49: 57-61.

15. Meisner M, Brunkhorst FM, Reith HB et al. Clinical experiences with a new semi-quantitative solid phase immunoassay for rapid measurement of procalcitonin. Clin Chem Lab Med 2000; 38: 989-995.

16. Al-Nawas B, Krammer I, Shah PM. Procalcitonin in diagnosis of severe infections. Eur J Med Res 1996; 1: 331-333.

17. Selberg O, Hecker H, Martin M et al. Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6. Crit Care Med 2000; 28: 2793-2798.

18. Tugrul S, Esen F, Celebi S et al. Reliability of procalcitonin as a severity marker in critically ill patients with inflammatory response. Anaesth Intensive Care 2002; 30: 747-754.

19. Wanner GA, Keel M, Steckholzer U et al. Relationship between procalcitonin plasma levels and severity of injury, organ failure, and mortality in injured patients. Crit Care Med 2000; 28: 950-957.

20. Zazula R, Průcha M, Spálený A et al. Prokalcitonin nejen v diferenciální diagnostice zánětlivé odpovědi organismu. Anest Neodkl Péče 2002; 13: 86-91.

21. Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta 2003; 328: 199.

22. Chýlková J, Procházková J. Baktericidní aktivita krve. In: Procházková J, John C, Lochman I et al. Vybrané diagnostické metody lékařské imunologie. Praha: Avicenum 1986, 209-211.

23. Bucová M. Určenie fagocytárnej schopnosti polymorfonukleárnych leukocytov. In: Buc M, Absolonová O, Bózner P et al. Praktické cvičenia z imunológie. Bratislava: Lekárska fakulta UK 1992: 38-41.

24. Assicot M, Gendrel D, Carsin H et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993; 341: 515-518.

25. Müller B, Becker KL, Schächinger H et al. Calcitonin precursors are reliable markers of sepsis in the medical intensive care unit. Crit Care Med 2000; 28: 977-983.

26. Ruokonen E, Ilkka L, Niskanen M et al. Procalcitonin and neopterin as indicators of infection in critically ill patients. Acta Anaesthesiologica Scandinavica 2002; 46: 398.

27. Russwurm S, Wiederhold M, Oberhoffer M et al. Molecular aspects and natural source of procalcitonin. Clin Chem Lab Med 1999; 37: 789-797.

28. Hoffman G, Czechowski M, Schobersberger W et al. Procalcitonin amplifies nitric oxide synthase gene expression and nitric oxide production in vascular smooth muscle. Crit Care Med 2002; 30: 2091-2095.

29. Wiedermann FJ, Kaneider N, Egger P et al. Migration of human monocytes in response to procalcitonin. Crit Care Med 2002; 30: 1112-1117.

30. Monneret G, Arpin M, Venet F et al. Calcitonin gene related peptide and N-procalcitonin modulate CD11b upregulation in lipopolysaccharide activated monocytes and neutrophils. Intensive Care Med 2003; 29: 923-928.

31. Bucová M, Záhorec R, Buc M. Immunosuppressive effect of recombinant human procalcitonin on mitogenic activity of lymphocytes. J End Res 2005, prijaté do tlače.

32. Bucová M. Úloha cytokínov v rozvoji lokálneho a systémového zápalu a septického šoku. Vnitř Lék 2002; 48: 755-762.

33. Bucová M. Polarizácia lymfocytov T a úloha cytokínov v iniciálnom procese rozvoja autoimunity. Rheumatologia 2002, 16: 117-124.

34. Murray PR (ed). Medical Microbiology. 3rd ed. New York: Mosby - Year Book, Inc. 1998: 109-114.

35. Fleischhack G, Kambeck I, Cipic D et al. Procalcitonin in pediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II. British Journal of Haematology 2000; 111: 1093.

36. Svaldi M, Hirber J, Lanthaler AI et al. Procalcitonin-reduced sensitivity and specificity in heavily leucopenic and immunosuppressed patients. British Journal of Haematology 2001; 115: 53.

37. Giamarellou H, Giamarellos-Bourboulis EJ, Repoussis P et al. Potential use of procalcitonin as a diagnostic criterion in febrile neutropenia: experience from a multicentre study. Clinical Microbiology & Infection 2004; 10: 628.

38. Bucová M. Prokalcitonín - prohormón, hormokín, mediátor zápalu, diagnostický a prognostický marker systémového zápalu. Československá fyziologie 2005; 54: 97.

39. Průcha M, Herold I, Zazula R et al. Srovnání prokalcitoninu, interleukinu 6 a C-reaktivního proteinu v diferenciální diagnostice pacientu JIP se syndromem sepse. Vnitř Lék 2003; 49: 541