title: Maternally administered melatonin differentially regulates lipopolysaccharide-induced proinflammatory and anti-inflammatory cytokines in maternal serum, amniotic fluid, fetal liver, and fetal brain.
abstract: Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including intra-uterine fetal death and intra-uterine growth retardation. In the LPS model, tumor necrosis factor alpha (TNF-alpha) is the major mediator leading to intra-uterine fetal death and intra-uterine growth retardation. Interleukin (IL)-10 protects rodents against LPS-induced intra-uterine fetal death and intra-uterine growth retardation. Melatonin is an immunomodulator. In the present study, we investigated the effect of maternally administered melatonin on LPS-induced proinflammatory and anti-inflammatory cytokines in maternal serum, amniotic fluid, fetal liver and fetal brain. The time pregnant mice were injected with melatonin [5.0 mg/kg, intraperitoneal (i.p.)] 30 min before LPS (500 microg/kg, i.p.) on gestational day 17. As expected, TNF-alpha, IL-1beta, IL-6 and IL-10 were obviously increased in maternal serum and amniotic fluid in response to LPS. In addition, maternal LPS exposure significantly increased the levels of TNF-alpha, IL-1beta, IL-6 and IL-10 in fetal liver, and TNF-alpha and IL-10 in fetal brain. Melatonin pretreatment significantly attenuated LPS-evoked elevation of TNF-alpha in maternal serum. On the contrary, melatonin aggravated LPS-induced increase in IL-10 in maternal serum. Melatonin had no effect on LPS-evoked IL-1beta and IL-6 in maternal serum and amniotic fluid. Interestingly, maternally administered melatonin also significantly attenuated LPS-evoked elevation of TNF-alpha in fetal brain, whereas the indole aggravated LPS-induced increase in IL-10 in fetal liver. Taken together, these results indicate that maternally administered melatonin differentially regulates LPS-induced proinflammatory and anti-inflammatory cytokines in maternal serum, amniotic fluid, fetal liver, and fetal brain.
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China. xudex@mail.hf.ah.cn
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Huan
authors.initials: H
authors.lastname: Ning
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism* / Q000502:physiology; D005333:Fetus; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy
chemical_list: D016207:Cytokines; D005326:Fetal Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008550:Melatonin