Kallikrein-kinin system in inflammatory bowel diseases: Intestinal involvement and correlation with the degree of tissue inflammation.
BACKGROUND
Tissue kallikrein and its natural inhibitor, kallistatin, play opposite roles in the generation of bradykinin, a potent mediator of inflammation. Observations on experimental models and humans with ulcerative colitis suggest a pathogenetic role of the kallikrein-kinin system in inflammatory bowel diseases.


OBJECTIVE
To evaluate tissue kallikrein and kallistatin in intestinal tissue samples from Crohn's disease and ulcerative colitis patients with different degrees of disease involvement.


METHODS
Full-thickness surgical intestinal samples were obtained from 144 subjects (38 normal controls, 32 inflammatory controls, 38 Crohn's disease, 36 ulcerative colitis) and tested for kallikrein and kallistatin by immunoperoxidase techniques.


RESULTS
Compared with controls, kallikrein immunoreactivity was significantly weaker in goblet cells (p=0.0001) and significantly stronger in interstitium (p=0.0001) of the Crohn's disease and ulcerative colitis samples. Kallistatin colocalised with kallikrein, with almost no reactivity in goblet cells but strong reactivity in interstitium of inflammatory bowel disease patients (p=0.0001 versus controls). The kallikrein and kallistatin depletion of goblet cells and the increased interstitial kallikrein and kallistatin reactivity correlated with the degree of tissue inflammation (p=0.0001). Disease-free samples had normal kallikrein and kallistatin patterns.


CONCLUSIONS
Kallikrein-kinin system is actively involved in inflammatory bowel disease as a result of the release of kallikrein in the intestinal extracellular space; this involvement correlates with the degree of tissue inflammation. The normal pattern observed in the disease-free samples seems to rule out a genetic defect of kallikrein and kallistatin in inflammatory bowel diseases.
Devani
M
M
Department of Internal Medicine, University of Milan, IRCCS Maggiore Hospital, Via Pace 15, 20122 Milan, Italy.
Vecchi
M
M
Ferrero
S
S
Avesani
E Contessini
EC
Arizzi
C
C
Chao
L
L
Colman
R W
RW
Cugno
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000032:analysis; D003106:Colon / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000473:pathology* / Q000503:physiopathology; D016234:Kallikrein-Kinin System; D007610:Kallikreins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015843:Serpins / Q000032:analysis
D002352:Carrier Proteins; D015843:Serpins; C051324:kallistatin; D007610:Kallikreins