抑鈣素原臨床應用

(1)

265 81

( procalcitonin; ProCT )

C ( CRP )

( biomarker )

( immunoneutralization )

( Procalcitonin;ProCT ) ( Biomarker )

( Immunoneutralization )

( ) (

SIRS )

( procalcitonin; ProCT )

1

C ( CRP )

( biomarker )

²

( immunoneutralization )

(2)

(ProCT)

Le Moullec 1984

11 6

14.5kDa

⁴

Broad

1989

⁵

Tabassian

6

1993 Assicot

7

( calci-

tonin; CT ) 116

( aminoacids )

C T - messenger RNA

( dipeptidase ) 114

immature

calcitonin ( ), aminoprocalci-

tonin calcitonin carboxypeptide-I ( CCP-I )

^1,8

immature calcitonin ( ProCT ) mature

calcitonin ( CT ) Mature cal-

citonin -

C

( C T p e p - t i d e s )

8

1-3

( parenchymal cells )

9

4

8 ( 2 5 3 0 )

9

( )

( cytokines ) ( IL-1 ,TNF-

, IL-6 )

^9,10

interferon-

9

- ( Kryptor PCT )

(

)

¹¹

0.06 g/L (

0.01 g/L ) 1 9

( serum ) ( plasma ) 20 50 l

1 0

0.5 g/L

( )

1 - 2 g / L 1 0 0 0

(3)

g / L

^{1 1}

0 . 5

g/L 0.1 g/L

( LUMItest PCT, Brahms )

0 . 3 0 . 5 g / L

^{1 2}

- - ( P C T - Q ,

BRAHMS ) 30

1 3

( )

1991 ( SIRS )

1 4

C ( CRP )

( )

( MODS ) ( MOF )

( cytokines ) TNF-

I L - 1 I L - 6

1 5

( ProCT )

1 - 3 , 1 6

ProCT ( g/L)

(4)

2 0 0 1

( s t a g i n g )

17

( )

1 0 %

11

7 5 %

¹¹

2004 Christ-Crain

L a n c e t

( Kryptor PCT )

11

( standard group )

( ProCT group ) 0 . 5 g / L

0.25 g/L

0 . 1 g / L

0.25 g/L 1 3

46.6%

1 9 8 7 A n t h o n i s e n N R

1 8

0 . 1 g / L 0 . 2 5 g / L

8 5 0 %

X X

1 2 5

( VAP )

D u f l o

(5)

1 9

L u y t 2 0 0 5

2 0

0 . 5 g / L

P a O

2

/ F I O

2

X

( )

C ,

2 3 Simon C

21

C

(1)

Chirouze 2002

22

0.4 g/L ( 98.8 % )

C ( ESR )

0 . 4 g / L

(2)

Viallon 2005

2 3

5 0 4 8

0.5 g/L

4.5 g/L ( 2.8-10.8

) 2

2.0 g/L ( 0.9-5.0 ) 4 5

3 4 4 8

p r o t e i n s , g l u c o s e , t o t a l polymorphonuclear leukocytes 48

B l a z e r

1 9 8 3

^{2 4}

2 4

C 2

3 2 4

(3)

Greaves 2003

25

5 0 0

43 10%

C

2 . 3 g/L

81% 85% 72%

9 2 % M u e l l e r 2 0 0 4

2 6

(6)

(4)

( translocation )

27,28

(5)

Benador 1998

( acute pyelonephritis ) ( lower UTI )

²⁹

5.37 g/L

0.38 g/L

C

P e c i l e 2004

30

(6)

31

TNF- TNF-

( )

Reith 1998

32

Meisner

(

) 1 0

g / L

^{3 3}

10 g/L Siassi

34

( )

E b e r h a r d 1 9 9 8

35

OKT3

Staehler 1997

36

( )

90%

³⁷

( 1 )

(7)

( 3 ) (2) ( cytokines )

( immunoneutra-

lization )

³

( translo- cation )

( 1 10 g/L )

4 8 1 g/L

2 4

7 0 0

Sorbera 2005 3

3 9

C R P (false-positive)

( )

(false-negative)

(8)

1.Whicher J, Bienvenu J, Monneret G. Procalcitonin as an acute phase marker. Ann Clin Biochem 2001; 38: 483-93.

2.Meisner M. Biomarkers of sepsis: clinically useful? Curr Opin Crit Care 2005; 11: 473-80.

3.Martinez JM, Becker KL, Muller B, et al. Improved phy- siologic and metabolic parameters and increased survival with late procalcitonin immunoneutralization in septic pigs. 41st Interscience Conference on Antimicrobial Agnest and Chemotherapy (ICAAC) 2001, Chicago, IL:

(abstract)

4.Le Moullec JM, Julliene A, Chenais J, et al. The complete se- quence of human preprocalcitonin. FEBS Lett 1984; 167: 93-7.

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

6.Tabassian AR, Nylen ES, Linoila IR, et al. Stimulation of ham- ster pulmonary neuroendocrine cells and associated peptides by repeated exposure to cigarette smoke. Am Rev Respir Dis 1989;

140: 436-40.

7.Assicot M, Gendrel D, Carsin H, et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993; 341: 515-8.

8.Muller Beat, Becker KL, Schachinger H, et al. Calcitonin pre- cursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 2000; 28: 977-83.

9.Linscheid P, Seboek D, Nylen ES, et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel pro- duct of human adipose tissue. Endocrinology 2003; 144: 5578- 84.

10.Meisner M. Pathobiochemistry and clinical use of procalcitonin.

Clin Chim Acta 2002; 323: 1702-9.

11.Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of procalcitonin -guided treatment on antibiotic use and out- come in lower respiratory tract infections: cluster-ran- domised, single-blinded intervention trial. Lancet 2004; 363:

600-7.

12.Snider RH, Nylen ES, Becker KL. Procalcitonin and i t s c o m p o n e n t p e p t i d e s i n s y s t e m i c i n f l a m m a t i o n : i m m u n o c h e m i c a l c h a r a c t e r i z a t i o n . J I n v e s t i g M e d 1997; 45: 552-60.

13.Meisner M, Brunkhorst FM, Reith HB, et al. Clinical experi- ences with a new semi-quantitative solid phase immunoassay for rapid measurement of procalcitonin. Clin Chem Lab Med 2000; 38: 989-95.

14.Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992; 101: 1644-55.

15.Harbarth S, Holeckova K, Froidevaux C, et al. Diagnostic va-

ly ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001; 164: 396-402.

16.Delevaux I, Andre M, Colombier M, et al. Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes? Ann Rheum Dis 2003; 62: 337-40.

17.Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ES- ICM/ACCP/ATS/SIS Internaltional Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-6.

18.Anthonisen NR, Manfreda J, Warren CP, et al. Antibiotic thera- py in exacerbations of chronic obstructive pulmonary disease.

Ann Intern Med 1987; 106: 196-204.

19.Duflo F, Debon R, Monneret G, et al. Alveolar and serum pro- calcitonin: diagnostic and prognostic value in ventilator-asso- ciated pneumonia. Anesthesiology 2002; 96: 74-9.

20.Luyt CE, Guerin V, Combes A, et al. Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 48-53.

21.Simon L, Gauvin F, Amre DK, et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a sys- temic review and meta-analysis. Clin Infect Dis 2004; 39: 206- 17.

22.Chirouze C, Schuhmacher H, Christian R, et al. Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis 2002; 35: 156- 61.

23.Viallon A, Guyomarch P, guyomarch S, et al. Decrease in serum procalcitonin levels over time during treatment of acute bacte- rial meningitis. Crit Care 2005; 9: 344-50.

24.Blazer S, Berant M, Alon U. Bacterial meningitis. Effect of an- tibiotic treatment on cerebrospinal fluid. Am J Clin Pathol 1983;

80: 386-7.

25.Greaves K, Mou D, Patel A, et al. Clinical criteria and the ap- propriate use of transthoracic echocardiography for the exclu- sion of infective endocarditis. Heart 2003; 89: 273-5.

26.Mueller C, Huber P, Laifer G, et al. Procalcitonin and the early diagnosis of infective endocarditis. Circulation 2004; 109: 1707- 10.

27.Lemprinen M, Puolackkannen P, Kemppainen F. Clinical value of severity markers in acute pancreatitis. Scand J Surg 2005; 94:

118-23

28.Rau B, Schilling MK, Beger HG. Laboratory markers of severe acute pancreatitis. Dig Dis 2004; 22: 247-57.

29.Benador N, Siegrist CA, Gendrel D, et al. Procalcitonin is a mar- ker of severity of renal lesions in pyelonephritis. Pediatrics 1998;

102: 1422-5.

30.Pecile P, Miorin E, Romanello C, et al. Procalcitonin: a marker of severity of acute pyelonephritis among children. Pediatrics 2004; 114: 249-54.

31.Davis TM, Assicot M, Bohuon C, et al. Serum procalcitonin con- centrations in acute malaria. Trans R Soc Trop Med Hyg 1994;

88: 670-1.

(9)

260-5.

33.Meisner M, Tschaikowsky K, Hutzler A, et al. Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med 1998; 24: 680-4.

34.Siassi M, Riese J, Steffensen R, et al. Mannan-binding lectin and procalcitonin measurement for prediction of postoperative in- fection. Crit Care 2005; 9: 483-9.

35.Eberhard OK, Langefeld I, Kuse ER, et al. Procalcitonin in the early phase after transplantation-will it all to diagnostic accura- cy? Clin Transplant 1998; 12: 206-11.

36.Staehler C, Hammer C, Meiser B, et al. Procalcitonin: A new marker for differential diagnosis of acute rejection and bacteri- al infection in heart transplantation. Transplant Proc 1997; 29:

584-5.

602. 38.Christ-Crain M, Muller B. Procalcitonin in bacterial infections- hype, hope, more or less? Swiss Med Wkly 2005; 135: 451-60.

39.Sorbera LA. Procalcitonin as an effective biomarker for the

diagnosis and prognosis of severe sepsis. Highlights from the

25th International Symposium on Intensive Care and Emergency

Medicine. March 21-25, 2005, Brussels, Belgium. Drugs Today

2005; 41: 253-6.

(10)

Clinical Applications of Procalcitonin ( ProCT )

Ching Huei Yang, and Daniel C.T. Lu

Many recent researches have demonstrated the efficacy of using the prohormone procalcitonin (ProCT) as a biomarker for severe sepsis. ProCT takes the advantage of its early and highly specific increase in response to clinically relevant bacterial infections and sepsis comparing with other parameters (such as CRP, WBC count).

It seems to be a promising tool to monitor the progression and the prognosis of the disease. Importantly, treat pa- tients with ProCT as a guide substantially will reduce antibiotic use and therefore prevent antibiotic overuse and the emerging resistant strains. Besides, immunoneutralization of ProCT is possible and it may open up a new therapeutic era for sepsis in the future. ( J Intern Med Taiwan 2006; 17: 1-10 )