The Role of Melatonin, IL-8 and IL-10 in Intrahepatic Cholestasis of
                    Pregnancy

Samettin Çelik; Huri Guve; Canan Çalışkan; Sebahattin Çelik

doi:10.1055/a-1233-9084

Zeitschrift für Geburtshilfe und Neonatologie, Table of Contents

Z Geburtshilfe Neonatol 2021; 225(03): 238-243
DOI: 10.1055/a-1233-9084

Original Article

The Role of Melatonin, IL-8 and IL-10 in Intrahepatic Cholestasis of Pregnancy

Samettin Çelik

¹Obstetrics and Gynecology, Samsun Education and Research Hospital, Samsun, Turkey

,

Huri Guve

²Department of Obstetrics and Gynecology, Düzce Üniversitesi Tip Fakültesi, Duzce, Turkey

,

Canan Çalışkan

¹Obstetrics and Gynecology, Samsun Education and Research Hospital, Samsun, Turkey

,

Sebahattin Çelik

³Obstetrics and Gynecology, Balıkesir Devlet Hastanesi, Balıkesir, Turkey

› Author Affiliations

Abstract

Introduction Intrahepatic cholestasis of pregnancy is a pregnancy-specific liver disease that usually emerges during the third trimester of pregnancy. It is characterized by itching and elevated serum total bile acid levels, and it may lead to severe fetal complications. This study aimed to investigate the role of interleukin-8, a pro-inflammatory cytokine; interleukin-10, an anti-inflammatory cytokine; and melatonin in intrahepatic cholestasis of pregnancy.

Materials and Methods This prospective, case-controlled study was conducted with 51 women with intrahepatic cholestasis of pregnancy (40 mild and 11 severe cases) and 43 healthy pregnant women. Serum interleukin-8, interleukin-10, and melatonin levels were evaluated.

Results Melatonin and interleukin -10 were significantly lower in subjects with intrahepatic cholestasis of pregnancy (p=0.001; p=0.001, respectively p<0.05). Interleukin-8 levels were found to be significantly higher in the cholestasis group than control group (p=0.001, p<0.05).

Conclusions Because interleukin-8, interleukin-10, and melatonin were found to be significantly correlated with intrahepatic cholestasis of pregnancy, we believe this finding could shed light on the etiology of the disease.

Key words

Intrahepatic cholestasis of pregnancy - melatonin - interleukin-8 - interleukin -10

Full Text

References

References
1 Floreani A, Gervasi MT. New insights on intrahepatic cholestasis of pregnancy. Clin Liver Dis 2016; 20: 177-189
2 Smith DD, Rood KM. Intrahepatic cholestasis of pregnancy. Clin Obstet Gynecol 2020; 63: 75-78
3 Lee RH, Goodwin TM, Greenspoon J. et al. The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population. J Perinatol 2006; 26: 527-532
4 Kondrackiene J, Kupcinskas L. Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems. World J Gastroenterol 2008; 14: 5781-5788
5 Ovadia C, Seed PT, Sklavounos A. et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet 2019; 393: 899-909
6 Langhans B, Krämer B, Louis M. et al. Intrahepatic IL-8 producing Foxp3 + CD4 + regulatory T cells and fibrogenesis in chronic hepatitis C. J Hepatol 2013; 59: 229-235
7 Zimmermann HW, Seidler S, Gassler N. et al. Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS One 2011; 6: e21381
8 Baggiolini M, Dewald B, Moser B. Human chemokines: an update. Annu Rev Immunol 1997; 15: 675-705
9 Ghasemi H, Ghazanfari T, Yaraee R. et al. Roles of IL-8 in ocular inflammations: a review. Ocul Immunol Inflamm 2011; 19: 401-412
10 Dong R, Zheng S. Interleukin-8: a critical chemokine in biliary atresia. J Gastroenterol Hepatol 2015; 30: 970-976
11 Ouyang W, Rutz S, Crellin NK. et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29: 71-109
12 Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010; 10: 170-181
13 Cretney E, Leung PS, Trezise S. et al. Characterization of Blimp-1 function in effector regulatory T cells. J Autoimmun 2018; 91: 73-82
14 Doherty DG. Immunity, tolerance and autoimmunity in the liver: a comprehensive review. J Autoimmun 2016; 66: 60-75
15 Zawilska JB, Skene DJ, Arendt J. Physiology and pharmacology of melatonin in relation to biological rhythms. Pharmacol Reports 2009; 61: 383-410
16 Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 1991; 12: 151-180
17 Bubenik GA. Gastrointestinal melatonin localization, function, and clinical relevance. Dig Dis Sci 2002; 47: 2336-2348
18 Nakamura Y, Tamura H, Kashida S. et al. Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. J Pineal Res 2001; 30: 29-33
19 Seron-ferre M, Valenzuela GJ, Torres-farfan C. Circadian clocks during embryonic and fetal development. Birth Defects Res. 2007 214(Part C): 204-214
20 Liu K, Zhou W, Li JH. Effects of melatonin on the expression of interleukin-8 and monocyte chemoattractant protein-1 in rats with TNBS-induced colitis. World Chinese Journal of Digestology 2008; 16: 1168-1172
21 Fuji T, Wang PL, Saito T. et al. Effects of melatonin on prostaglandin E2-induced proinflammatory cytokine production in human gingival fibroblasts. Journal of Hard Tissue Biology 2004; 13: 24-28
22 Ersoy ÖF, Özkan N. Özsoy et al. Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model. Ulus Travma Acil Cerrahi Derg 2016; 22: 315-321
23 Kirbas A, Biberoglu E, Daglar K. et al. Neutrophil-to-lymphocyte ratio as a diagnostic marker of intrahepatic cholestasis of pregnancy. Eur J Obstet Gynecol Reprod Biol 2014; 180: 12-15
24 Kirbas A, Biberoglu E, Ersoy AO. et al. The role of interleukin-17 in intrahepatic cholestasis of pregnancy. J Matern Neonatal Med 2016; 29: 977-981
25 Yayi H, Danqing W, Shuyun L. et al. Immunologic abnormality of intrahepatic cholestasis of pregnancy. Am J Reprod Immunol 2010; 63: 267-273
26 Matsushima K, Oppenheim JJ. Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL 1 and TNF. Cytokine 1989; 1: 2-13
27 Zhang Y, Pan Y, Lin C. et al. Bile acids evoke placental inflammation by activating Gpbar 1 / NF- κ B pathway in intrahepatic cholestasis of pregnancy. J Mol Cell Biol 2016; 8: 530-541
28 Chatterjee P, Chiasson VL, Bounds KR. et al. Regulation of the anti-inflammatory cytokines interleukin-4 and interleukin-10 during pregnancy. Front Immunol 2014; 5: 1-6
29 Cao LQ, Qu GD, Wang DM. Expression profiles of IL-10, TNF-a, and SOCS3 in placenta of pregnant women with intrahepatic cholestasis. Chinese. J Hepatol 2012; 20: 935-938
30 Zhang LJ, Li MY. Expression of suppressor of cytokine signaling 3 and its significance in human placenta with pregnant intrahepatic cholestasis. Zhonghua Fu Chan Ke Za Zhi 2010; 45: 406-410
31 Voiculescu SE, Zygouropoulos N, Zahiu CD. et al. Role of melatonin in embryo fetal development. J Med Life 2014; 7: 488-492
32 Carrillo-Vico A, Lardone PJ, Álvarez-Sánchez N. et al. Melatonin: buffering the immune system. Int J Mol Sci 2013; 14: 8638-8683
33 Colares JR, Schemitt EG, Hartmann RM. et al. Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation. World J Gastroenterol 2016; 22: 8918-8928
34 Chen L, Zhou T, Wu N. et al. Pinealectomy or light exposure exacerbates biliary damage and liver fibrosis in cholestatic rats through decreased melatonin synthesis. Biochim Biophys Acta Mol Basis Dis 2019; 1865: 1525-1539
35 Kim GD, Lee SE, Kim TH. et al. Melatonin suppresses acrolein-induced IL-8 production in human pulmonary fibroblasts. J Pineal Res 2011; 52: 356-364
36 Chen S, Huang S, Chen J. et al. Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis. Int Immunopharmacol 2016; 31: 169-177