Calcitonin precursors: early markers of gut barrier dysfunction in patients with acute pancreatitis.
BACKGROUND
Severe acute pancreatitis is associated with an early increase in intestinal permeability and endotoxemia. Endotoxin is a potent stimulator for the production and release of procalcitonin and its components (calcitonin precursors; [CTpr]). The aim of this study is to evaluate the role of plasma CTpr as an early marker for gut barrier dysfunction in patients with acute pancreatitis.


METHODS
Intestinal permeability to macromolecules (polyethylene glycol 3350), serum endotoxin and antiendotoxin core antibodies, plasma CTpr, and serum C-reactive protein (CRP) were measured on admission in 60 patients with acute pancreatitis. Attacks were classified as mild (n = 48) or severe (n = 12) according to the Atlanta criteria.


RESULTS
Compared with mild attacks of acute pancreatitis, severe attacks were significantly associated with an increase in intestinal permeability index (median: 0.02 vs. 0.006, P < 0.001), the frequency of endotoxemia (73% vs. 41%, P = 0.04), and the extent of depletion of serum IgM antiendotoxin antibodies (median: 43 MMU vs. 100 MMU, P = 0.004). Plasma CTpr levels were significantly elevated in patients with severe attacks compared with mild attacks on both the day of admission and on day 3 (median: 64 vs. 22 fmol/mL, P = 0.03; and 90 vs. 29 fmol/mL, P = 0.003 respectively). A positive and significant correlation was observed between the admission serum endotoxin and plasma CTpr levels on admission (r = 0.7, P < 0.0001) and on day 3 (r = 0.96, P < 0.0001), and between plasma CTpr on day 7 and the intestinal permeability index (r = 0.85, P = 0.0001). In contrast, only a weak positive correlation was observed between peak serum levels of CRP and plasma CTpr on admission (r = 0.3, P = 0.017) and on day 7 (r = 0.471, P = 0.049), as well as between CRP and each of the admission serum endotoxin (r = 0.3, P = 0.03) and the intestinal permeability index (r = 0.375, P = 0.007).


CONCLUSIONS
In patients with acute pancreatitis, plasma concentrations of CTpr appear to reflect more closely the derangement in gut barrier function rather than the extent of systemic inflammation.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D019446:Endotoxemia / Q000097:blood / Q000150:complications / Q000503:physiopathology; D004731:Endotoxins / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D007422:Intestines / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D010539:Permeability; D011092:Polyethylene Glycols; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood*
D000906:Antibodies; D015415:Biomarkers; C000606589:CALCA protein, human; D004731:Endotoxins; D011498:Protein Precursors; D011092:Polyethylene Glycols; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide