Ursodeoxycholic acid (UDCA) suppresses liver interleukin 2 mRNA in the cholangitis model.
OBJECTIVE
Ursodeoxycholic acid (UDCA) is used globally as the drug of first choice for the treatment of primary biliary cirrhosis (PBC). The mechanism by which UDCA exerts its effect has been clarified mainly by in vitro studies. However, no other studies have so far been successful in defining the expression profiles of relevant cytokines in experimental PBC models.


METHODS
In this study, we established an immune-mediated cholangitis mouse model by immunizing mice with an intraperitoneal injection of carbonic anhydrase (CA)-II every other week, for a total of three injections. After the administration of UDCA, the animals were examined for the hepatic histopathology and liver enzyme levels in the serum, as well as the cytokine mRNA contents in the liver.


RESULTS
After the administration of UDCA, peribiliary cell invasion decreased, but the change of hepatic enzyme was not observed. The quantities of interleukin (IL)-2 mRNA in the liver were all elevated in the CA-II group as compared with the control group in a semiquantitative assay. The quantities of IL-2 mRNA were significantly decreased in the CA-II+UDCA group compared with the CA-II group. UDCA suppressed the production of IL-2 and had the tendency to suppress the production of IL-4, and the suppression of IL-2 was predominant, compared to the suppression of IL-4, but UDCA did not significantly effect the expression of interferon (IFN)-gamma mRNA, IL-6 mRNA, IL-10 mRNA.


CONCLUSIONS
UDCA predominantly suppressed IL-2 mRNA compared to IL-4 mRNA in the liver of the cholangitis model. The results partially clarified the mechanism by which UDCA exerts its effect on PBC.
Miyaguchi
Shingo
S
Department of Internal Medicine, Harunaso Hospital, Japan.
Mori
Masaya
M
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D024402:Carbonic Anhydrase II / Q000276:immunology; D002761:Cholangitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D005260:Female; D007114:Immunization; D007376:Interleukin-2 / Q000235:genetics*; D007931:Leucyl Aminopeptidase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000637:Transaminases / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D014580:Ursodeoxycholic Acid; D000637:Transaminases; D000469:Alkaline Phosphatase; D007931:Leucyl Aminopeptidase; D024402:Carbonic Anhydrase II