Immunomodulatory effects of ursodeoxycholic acid on immune responses

Abstract

Ursodeoxycholic acid was recently recognized as an effective agent in the treatment of primary biliary cirrhosis. Experimental evidence supporting the usefulness of ursodeoxycholic acid as a potentially beneficial therapeutic agent for primary biliary cirrhosis has been reported from the biochemical and physiological aspects. In this study, we investigated the direct effects of ursodeoxycholic acid on immunoglobulin and cytokine production in vitro using plaque-forming cell assay and enzyme-linked immunosorbent assay. It was demonstrated that ursodeoxycholic acid suppressed the production of IgM, IgG and IgA induced by Staphylococcus aureus Cowan I in peripheral blood mononuclear cells derived from healthy subjects and patients with primary biliary cirrhosis and also in human B lymphoma cell lines. Furthermore, ursodeoxycholic acid suppressed interleukin-2 and interleukin-4 production induced by concanavalin A and interferon-gamma production induced by polyinosinic-polycytidylic acid, but it did not affect interleukin-1 and interleukin-6 production induced by lipopolysaccharide in peripheral blood mononuclear cells. In addition, ursodeoxycholic acid suppressed the concanavalin A-induced thymocyte proliferation mediated by interleukin-1. Cytotoxicity against lymphocytes was not observed at the concentrations of ursodeoxycholic acid used. These results suggest that the beneficial effect of ursodeoxycholic acid in primary biliary cirrhosis is mediated in part by immunosuppression.

A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis-associated liver disease

“…An immunomodulatory effect of UDCA, with reduced production in vitro of IgM, IgG, IgA, and cytokines by peripheral mononuclear cells, has been reported. 42,43 It was therefore interesting to note the significant decrease of IgG after 24 months, as has previously been shown during UDCA treatment of patients with primary biliary cirrhosis. 8 The urinary bile acid profile confirmed compliance and showed an increased excretion of UDCA and its metabolites similar to what has been reported in other liver diseases.…”

T Helper–Cell Phenotype Regulates Atherosclerosis in Mice Under Conditions of Mild Hypercholesterolemia

“…Bile salts, in particular ursodeoxycholate, in high quantities are known to have effects on the immune system. 32 Although it is unlikely that the levels achieved by ingesting the relatively small amounts used in chow are of major importance, we cannot rule this out completely as a possible source of error.…”

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

“…UDCA has been shown to displace hydrophobic endogenous bile acids associated with increased cell membrane fluidity and permeability and with increased secretion of bile acids and other organic compounds. 31 Moreover, UDCA has been shown to be immunomodulatory, 32 and in primary biliary cirrhosis it reduces the overexpression of hepatocellular and biliary expression of major histocompatibility complex Class I and II molecules, 33,34 unlike cyclosporin or corticosteroids. 35 In PSC, UDCA therapy at 13 to 15 mg/kg/d has been associated with significant improvement in biochemical test results 13,36 but has not been shown to have any effect on symptoms, liver histology, or time to transplantation.…”