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.

Keywords:

• Intrahepatic cholestasis in pregnancy
• inflammatory cytokine
• interleukin
• tumor necrosis factor

Acknowledgements

The authors express our appreciation to the Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine for help with patient recruitment and sample collection.

Author contributions

Liu Y and Huang SJ proposed and designed the study; Liu XS and Huang SJ collected data; Guo FN and Li GH analyzed and interpreted data; Liu Y and Huang SJ drafted the manuscript; Du QL and Liu Y reviewed and edited the manuscript; Du QL provided administrative support and funding acquisition; Liu Y and Huang SJ contributed equally to this work. All authors read, revised and approved the final draft.

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

This work was supported by the Shanghai Science and Technology Commission, No.20Y11907900; the Technology Project of Shanghai Pudong New District Health and Family Planning Commission, No. PW2019D-9.