Elevations in IFN-gamma, IL-5, and IL-10 in patients with the autoimmune disease primary biliary cirrhosis: association with autoantibodies and soluble CD30

Abstract

Antimitochondrial antibodies (AMA) which recognize the E2 component of the pyruvate dehydrogenase complex are found in virtually all patients with the autoimmune liver disease primary biliary cirrhosis (PBC). The factors that contribute to elevated AMA and the relationship of the autoantibodies to disease pathogenesis have not been elucidated. Since cytokines are important regulators of antibody production and isotype switching, the association of specific cytokines to antibody production was examined in patients with PBC. Elevations in IL-2, IFN-gamma, IL-4, IL-5, and IL-10 were detected in serum from patients with PBC. However, only IFN-gamma (6012 +/- 1128 pg/ml vs 147 +/- 89 pg/ml, P < 0.0001) and IL-5 (382 +/- 103 pg/ml vs 29 +/- 12 pg/ml, P < 0.001) were significantly elevated compared to normal controls. Moreover, there was a positive correlation in the levels of IFN-gamma, and to a lesser extent IL-5, with the levels of soluble CD30 (sCD30) in the circulation. The elevated levels of sCD30 detected in patients with PBC (194 +/- 29 U/ml vs 39 +/- 9 U/ml in normal controls) suggest that CD30+ cells may produce cytokines, which contribute to the immune abnormalities in patients with PBC.