Antiproteasic activity of C1 inhibitor. Therapeutic perspectives.
Kallikrein is a protease involved in the inflammatory process causing acute pancreatitis. Attempts to prevent this process with antiprotease agents have been successful in experimental animal models but disappointing in humans. We studied 40 consecutive patients undergoing endoscopic papillosphincterotomy. This procedure can induce a transient, moderate pancreatic inflammatory reaction, characterized by hyperamylasemia, which in 1-6% of the patients may evolve to acute pancreatitis. To assess the capacity of C1 inhibitor, the main physiological inhibitor of kallikrein, to prevent such complications, we pretreated 20 patients with 3000 U of C1 inhibitor plasma concentrate i.v.; 20 patients served as controls. Serum levels of amylase and functional C1 inhibitor were determined before the procedure and after 2, 4, 8 and 24 hours. Serum levels of amylase in the control group (146 +/- 21 IU) and in the group treated with C1 inhibitor (158 +/- 25 IU) were similar before treatment. Four and 8 hours after the end of the procedure, amylase levels were significantly lower (p < 0.001) in the treated group (231 +/- 46 and 355 +/- 104 IU) than in the control subjects (969 +/- 229 and 923 +/- 207 IU). After 24 hours both groups had normal amylase levels. In treated patients, functional levels of C1 inhibitor increased from 104 +/- 30 to 175 +/- 30% and remained elevated throughout the observation period. These data indicate that C1 inhibitor plasma concentrate can prevent hyperamylasemia following pancreas injury, probably, by inhibiting the kallikrein-mediated inflammatory process. C1 inhibitor might benefit patients at high risk of pancreatitis who undergo endoscopic papillosphincterotomy.
Cicardi
M
M
Istituto di Medicina Interna, Università degli Studi, Ospedale Maggiore di Milano.
Testoni
P
P
Bergamaschini
L
L
Guzzoni
S
S
Cugno
M
M
Buizza
M
M
Bagnolo
F
F
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000681:Amylases / Q000097:blood*; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000517:prevention & control; D011480:Protease Inhibitors; D016717:Sphincterotomy, Endoscopic; D013997:Time Factors
D003174:Complement C1 Inactivator Proteins; D011480:Protease Inhibitors; D000681:Amylases; D007610:Kallikreins