Stimulation with minimal amounts of IL-12 (0.005 ng/ml) led to significant upregulation of CXCR6 (<i>p</i> < 0.005), and enhanced IFNγ production (<i>p</i> < 0.02) on NK cells from PBC patients compared to individuals with non-autoimmune chronic liver disease, indicating dysregulation of the IL-12/STAT4 axis.
Lower plasma IL-35 levels were accompanied by higher levels of typical clinical parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such as interferon-gamma (IFN-γ), in PBC patients (P < 0.05 for each).
In the liver of patients with PBC (n = 7) a significantly higher proportion of IL-12Rβ2<sup>+</sup>Tregs (16% on average) was detected (p < 0.05) compared to other liver disease controls (5%)(n = 18) which also showed ex vivo high IFNG and TBET expression.
Expression analysis of CNSDC lesions in stage I PBC showed the presence of active inflammatory changes, characterized by the significant elevation of interferon-gamma and the development and maturation of lymphocytes.
In the present study, we measured plasma levels of chemokines interferon-gamma-inducible protein-10 (IP-10) and monokine induced by gamma interferon (MIG), and also studied the expression of CXCR3 chemokine receptors in 105 subjects, including 53 patients with PBC, 26 first degree relatives and 26 healthy controls.
Moreover, IFN-gamma mRNA expression was more commonly detected than IL-4 expression in PBC livers, and the levels of IFN-gamma mRNA expression were highly correlated with the degree of portal inflammatory activity.
The results suggest that: (i) there may be fundamental differences in the roles that cytokines play in the hepatic inflammatory processes of PBC and CHB; and (ii) while hepatic IFN-gamma mRNA expression is not specific for PBC, IFN-gamma may play a prominent role in the immunopathogenesis of PBC.
IL-1 beta and interferon gamma mRNA showed increased expression in cirrhotics with autoimmune chronic active hepatitis compared with those with primary biliary cirrhosis.