In experiments involving human volunteers injected with
Escherichia coli toxin, subjects described symptoms of
chills, fever, rigors and myalgia within 1–3 hours. PCT
concentrations started to rise at 4 hours, peaked at 6 hours
and then plateaued at 8–24 hours.In comparison with
other inflammatory markers, PCT peaked after TNF-a (90
minutes) and IL-6 (3 hours). However, these cytokines
returned to baseline after only 6 and 8 hours, respectively,
giving them a relatively narrow testing window to be useful.
C-reactive protein (CRP), which takes 12–24 hours to rise
and 20–72 hours to plateau, remains elevated for 3–7 days.
This is longer than the 2–3 days it takes PCT concentrations
to normalise, offering PCT a natural advantage in
CRP
was so named because it was first discovered as a substance in the serum of patients with acute inflammation that reacted with the C- (capsular) polysaccharide of pneumococcus.Discovered by Tillett and Francis in 1930 , it was initially thought that CRP might be a pathogenic secretion as it was elevated in people with a variety of illnesses including cancer, however, discovery of hepatic synthesis demonstrated that it is a native protein.
The CRP gene is located on the first chromosome (1q21-q23).
CRP is a 224-residue protein[9] with a monomer molar mass of 25106 Da.
The protein is an annular pentameric disc in shape and a member of the small pentraxins family.
Function
The acute phase response develops in a wide range of acute and chronic inflammatory conditions like bacterial, viral, or fungal infections; rheumatic and other inflammatory diseases; malignancy; and tissue injury or necrosis.
These conditions cause release of interleukin-6 and other cytokines that trigger the synthesis of CRP and fibrinogen by the liver.
During the acute phase response, levels of CRP rapidly increase within 2 hours of acute insult, reaching a peak at 48 hours.
With resolution of the acute phase response, CRP declines with a relatively short half-life of 18 hours.
Measuring CRP level is a screen for infectious and inflammatory diseases.
Rapid, marked increases in CRP occur with inflammation, infection, trauma and tissue necrosis, malignancies, and autoimmune disorders. Because there are a large number of disparate conditions that can increase CRP production, an elevated CRP level does not diagnose a specific disease.
The physiological role of CRP is to bind to phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system. CRP binds to phosphocholine on microbes and damaged cells and enhances phagocytosis by macrophages.
Thus, CRP participates in the clearance of necrotic and apoptotic cells.
CRP
is a member of the class of acute-phase reactants, as its levels rise dramatically during inflammatoryprocesses occurring in the body.
This increment is due to a rise in the plasma concentration of IL-6, which is produced predominantly by
macrophages[2] as well as adipocytes.[3]
CRP binds to phosphocholine on microbes. It is thought to assist in complement binding to foreign and damaged cells and enhances phagocytosis by macrophages (opsonin mediated phagocytosis), which express a receptor for CRP.
It is also believed to play another important role in innate immunity, as an early defense system against infections.
CRP rises up to 50,000-fold in acute inflammation, such as infection. It rises above normal limits within 6 hours, and peaks at 48 hours. Its half-life is constant, and therefore its level is mainly determined by the rate of production (and hence the severity of the precipitating cause).
Clinical significance
Elevations of CRP in the absence of clinically significant inflammation can occur in renal failure.
CRP level is an independent risk factor for atherosclerotic disease.
Patients with high CRP concentrations are more likely to develop stroke, myocardial infarction, and severe peripheral vascular disease.
A high-sensitivity
CRP
(hs-CRP) test measures low levels of CRP using laser
nephelometry
.
The test gives results in 25 minutes with a sensitivity down to 0.04 mg/L.
Normal concentration in healthy human serum is usually lower than 10 mg/L, slightly increasing
with
aging
.
Higher levels are found in late
pregnant
women, mild inflammation and viral infections (10–
40 mg/L), active inflammation, bacterial infection (40–200 mg/L), severe
bacterial infections
and
burns
(>200 mg/L).
[22]CRP
is a more sensitive and accurate reflection of the acute phase response than the VES.
The half-life of CRP is constant.
Therefore,
CRP
level is mainly determined by the rate of production (and hence the severity of
the precipitating cause).
In the first 24 h, VES may be normal and CRP elevated.
La calcitonina (32 aa) ed i suoi precursori si dimostrarono elevati nei pazienti affetti da neoplasie di
origine neuroendocrina,quelle a cellule C della tiroide;da neoplasia polmonare a piccole cellule o da
tumori carcinoidi.
Successivamente i precursori della Calcitonina,Procalcitonina inclusa (116 aa) si dimostrarono
notevolmente elevati nel siero di pazienti che versavano in uno stato di grave infiammazione
sistemica:danno polmonare da inalazione o da aspirazione,ustioni,pancreatite,infarto
mesenterico,trauma multiplo,chirurgia maggiore.
Nel 1983 elevati valori di PCT furono riportati in corso di malattie infettive e più tardi anche nella sepsi.
In questo caso la fonte principale di PCT risultarono essere le cellule parenchimali non neuroendocrine di
tutti gli organi,che non disponevano inoltre della capacità di trasformare il precursore nella sua forma
definitiva.
Questo fenomeno fu attribuito allo stimolo derivato dalla traslocazione batterica di lipopolisaccaride o
altre componenti batteriche o ad uno stimolo di carattere proinfiammatorio il TNFα.
Questo ha creato non poche difficoltà sia in letteratura che nella pratica nella valutazione di un paziente
con iper ProPCT.
Infiammazione sistemica senza infezione
Valori molto elevati indifferenziabili da quelli riscontrati in corso di sepsi. Lipopolisaccaride o altri prodotti batterici?
Grave trauma
valori elevati in pazienti non infetti :
Aumento entro 2 – 4 ore con picco 1^ - 2^ giornata : da 2 – 3 fino a 10 – 20 ng/ml Valori precocemente elevati predicono MOF
Valori persistentemente elevati o un secondo picco:infezione o sepsi
Chirurgia maggiore
valori precocemente elevati di ProPCT indipendentemente da infezione o sepsi
Valori iniziali molto elevati o persistenti o 2° picco possono preannunciare infezione o sepsi
Ustioni
1 studio: a 24 ore: valori da indeterminabili a 350 ng/ml
Infezioni “localizzate” Polmoniti batteriche
1 studio : 35 pz.: ProPCT vm 19.5 ng/ml;2° studio vp 62 ng/ml. Polmoniti associate a batteriemia tendono ad avere valori più elevati
Infezioni vie urinarie
Valori fino a 10 ng/ml
Sepsi o infezioni gravi
I valori variano entro un range molto ampio pari a 10
2– 10
3Valori soglia > 2 ng/ml
< 2 ng/ml meno probabile
0,4 0,5 ng/ml improbabile
Nonostante ciò pazienti con diagnosi di infezione grave o sepsi hanno livelli < 2ng/ml fino a < 0,5 ng/ml
Considerando un sostanziale overlap dei valori i pazienti con sepsi hanno valori superiori rispetto a quelli
con SIRS e pazienti con sepsi severa e shock settico esibiscono i valori massimi.
Valore prognostico
Valori elevati nelle fasi iniziali hanno significato prognostico negativo.
ProPCT è solo una delle molte variabili per valutare la gravità della malattia:
Valori estremamente elevati: paziente più malato con prognosi più sfavorevole.
Ma è vero anche il contrario.
Per ciascun range : valori singoli o occasionale creano confusione:conta di più il trend.
La persistenza di valori elevati : rischio decesso La riduzione : > probabilità di sopravvivenza Anche qui risultati non univoci.
Batteriemia valori più elevati Gram negativi valori più elevati
