Effect of ursodeoxycholic acid on inflammatory infiltrate in gallbladder muscle of cholesterol gallstone patients.
BACKGROUND
Reduced gallbladder (GB) contractility and chronic inflammatory changes in the mucosa have been reported in patients with cholesterol gallstones (GS). Ursodeoxycholic acid (UDCA) restores GB contractility and antagonises liver macrophage activation. In the colon, hydrophobic bile acid, not hydrophilic UDCA, induces mast cell degranulation. We studied the presence of monocyte/macrophage infiltrate, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, the number of total and degranulated mast cells in the GB muscle layer of cholesterol GS patients, and the effect of UDCA administration.


METHODS
Gallbladder tissue was obtained from cholesterol GS patients, either treated or untreated with UDCA (10 mg kg(-1) day(-1)) for 30 days prior to surgery. Gallbladders removed for neoplastic diseases, not involving GB, were evaluated for control purposes. The presence of monocytes/macrophages (CD68 positive), granulocytes, and mast cells, and the COX-2 and iNOS expression, was determined immunohistochemically.


RESULTS
The number of CD68, granulocytes, mast cells, COX-2 and iNOS positive cells was significantly higher in the muscle layer of GS patients than in controls. Compared to untreated patients, those treated with UDCA showed significantly lower levels of CD68, COX-2 positive cells and degranulated mast cells and a lesser number of iNOS positive cells and granulocytes.


CONCLUSIONS
An inflammatory monocyte/macrophage, mast cell and granulocyte infiltrate is present in the GB muscle layer of GS patients. Ursodeoxycholic acid decreases macrophages, degranulated mast cells and COX-2 expression. These results suggest that monocytes/macrophages and degranulating mast cells contribute to muscle cell dysfunction in cholesterol GS patients and support the anti-inflammatory effect of UDCA.
Carotti
S
S
Department of Biomedical Research (CIR), University Campus Bio-Medico, Rome, Italy.
Guarino
M P L
MP
Cicala
M
M
Perrone
G
G
Alloni
R
R
Segreto
F
F
Rabitti
C
C
Morini
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002784:Cholesterol / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005704:Gallbladder / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D042882:Gallstones / Q000737:chemistry*; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002756:Cholagogues and Choleretics; D002784:Cholesterol; D051546:Cyclooxygenase 2; D052247:Nitric Oxide Synthase Type II; D014580:Ursodeoxycholic Acid; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496319:NOS2 protein, human; C496540:PTGS2 protein, human