Serum profiles of inflammatory cytokines associated with intrahepatic cholestasis of pregnancy

Abstract

Background: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is not clear, and some researchers have compared the differences in serum levels of inflammatory cytokines between ICP patients and normal pregnant women, but there are few studies and different conclusions. Aim: To investigate the levels of inflammatory cytokines such as interleukins (IL) −4, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) in patients with ICP and their potential role in pathophysiology. Methods: This case-control study was conducted in Shanghai First Maternity and Infant Health Hospital, and we recruited ICP patients and age-matched healthy pregnant women as a control group. Plasma samples from 40 subjects with ICP and 40 subjects without ICP were tested for concentration of the following inflammatory cytokines: interferon-gamma, IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α. Analyzed inflammatory cytokines were then assessed, either individually or in combination with regard to ICP. Results: The cytokine composition of the ICP and CTL group was significantly different. We compared levels of inflammatory cytokines with regard to the presence of ICP symptoms. Levels of IL-4, IL-6, and TNF-α were significantly lower in ICP subjects, and IL-8 were significantly higher in ICP subjects, compared with CTL subjects. The TNF-α showed the best performance for ICP identification (area under the curve [AUC]: 0.829). Performance was increased when TNF-α was combined with IL-4 and IL-8 analysis (AUC, 0.901). Spearman correlation and linear regression analysis revealed that the TNF-α concentrations correlated with IL-4 and IL-6 levels, and inversely correlated to TBA, ALT, AST, and IL-8 levels. Conclusion: IL-4, IL-6, and TNF-α were significantly decreased, while IL-8 was significantly increased in the ICP group compared with the healthy control group. TNF showed the best single marker discriminatory potential; however, combining TNF-α, IL-4, and IL-8 analyses increased performance for ICP identification.