Altered Placental Development in Interleukin-10 Null Mutant Mice

Roberts, Claire; White, Catherine A.; Nicolas, Wiemer; Ramsay, Alistair J.; Robertson, Sarah A.

doi:10.1053/plac.2002.0949

Cited by 42 publications

(37 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The explanation for this likely relates to placental structure and function, with IL-10 constraining development of the placental labyrinth compartment where maternal-fetal nutrient exchange occurs, partly through inhibiting vasodilation of the fetal-placental circulation (59). It is possible that an effect on placental blood flow underpins the failure of exogenous IL-10 administration to alleviate the LPS-induced fetal growth restriction seen in the current study.…”

Section: Discussionmentioning

confidence: 77%

“…This effect might be elicited through IL-10 down-regulation of placental production of NO (28), a key regulator of vasodilation and hemodynamics of the fetal and placental vasculature thought to be critical in maintaining nutrient and oxygen delivery to the fetus (60). Although IL-10 can also influence cytotrophoblast differentiation and invasiveness, it seems unlikely that changes in cell composition would account for effects of IL-10 in the placenta late in pregnancy when its morphogenesis is complete (59). The lack of benefit of IL-10 treatment for fetal mass contrasts with previous experiments in rats where LPS-induced fetal growth restriction was alleviated with exogenous IL-10 supplied at similar doses (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…However, caution is warranted in view of the expected high variation in patient responsiveness and the potential for unintended downstream immune-modulating effects of this cytokine (62). Given the potential effects of IL-10 in restricting placental function and fetal growth in mice (33,59), the possibility of adverse effects of sustained IL-10 administration on the fetus also would need to be considered.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice

Robertson

Skinner

Care

2006

The Journal of Immunology

177

139

View full text Add to dashboard Cite

IL-10 is highly expressed in the uterus and placenta and is implicated in controlling inflammation-induced pathologies of pregnancy. To investigate the role of IL-10 in regulating preterm labor, the response of IL-10 null mutant mice to low-dose LPS in late gestation was evaluated. When IL-10 null mutant C57BL/6 (IL-10−/−) and control (IL-10+/+) mice were administered LPS on day 17 of pregnancy, the dose of LPS required to elicit 50% preterm fetal loss was 10-fold lower in IL-10−/− mice than in IL-10+/+ mice. Surviving fetuses in IL-10−/− mice exhibited fetal growth restriction at lower doses of LPS than IL-10+/+ mice. Marked elevation of LPS-induced immunoactive TNF-α and IL-6 was evident in the serum, uterus, and placenta of IL-10−/− mice, and TNF-α and IL-6 mRNA expression was elevated in the uterus and placenta, but not the fetus. Serum IL-1α, IFN-γ, and IL-12p40 were increased and soluble TNFRII was diminished in the absence of IL-10, with these changes also reflected in the gestational tissues. Administration of rIL-10 to IL-10−/− mice attenuated proinflammatory cytokine synthesis and alleviated their increased susceptibility to preterm loss. Exogenous IL-10 also protected IL-10+/+ mice from fetal loss. These data show that IL-10 modulates resistance to inflammatory stimuli by down-regulating proinflammatory cytokines in the uterus and placenta. Abundance of endogenous IL-10 in gestational tissues is therefore identified as a critical determinant of resistance to preterm labor, and IL-10 may provide a useful therapeutic agent in this common condition.

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice

Robertson

Skinner

Care

2006

The Journal of Immunology

177

139

View full text Add to dashboard Cite

show abstract

“…As mentioned previously, T reg play an important role in maintaining tolerance during pregnancy while suppressing the activity of inflammatory Th17 cells, which have been implicated in autoimmune tissue injury. Here it can be appreciated that IL-6 expression, the result of MIA, can promote the expression of Th17 cells while downregulating T reg expression compromising placental function while promoting a potential autoimmune response to the developing fetus [144,[149][150][151] . Observations of an increase in maternal antibodies against neuronal and lymphocytic markers in the serum of mothers of autistic children further strengthen this hypothesis, suggesting the involvement of a maternal immune response in precipitating this disorder [71,110] .…”

Section: Mia and The Placental Barriermentioning

confidence: 99%

Maternal Immune Activation and Autism Spectrum Disorder: Interleukin-6 Signaling as a Key Mechanistic Pathway

Parker-Athill¹,

Tan²

2010

Neurosignals

126

105

View full text Add to dashboard Cite

An emerging area of research in autism spectrum disorder (ASD) is the role of prenatal exposure to inflammatory mediators during critical developmental periods. Epidemiological data has highlighted this relationship showing significant correlations between prenatal exposure to pathogens, including influenza, and the occurrence of ASD. Although there has not been a definitive molecular mechanism established, researchers have begun to investigate this relationship as animal models of maternal infection have support- ed epidemiological findings. Several groups utilizing these animal models have found that activation of the maternal immune system, termed maternal immune activation (MIA), and more specifically the exposure of the developing fetus to maternal cytokines precipitate the neurological, immunological and behavioral abnormalities observed in the offspring of these animals. These abnormalities have correlated with clinical findings of immune dysregulation, neurological and behavioral abnormalities in some autistic individuals. Additionally, researchers have observed genetic variations in these models in genes which regulate neurological and immunological development, similar to what is observed clinically in ASD. Altogether, the role of MIA and cytokine dysregulation, as a key mediator in the neuropathological, behavioral and possibly genetic irregularities observed clinically in autism are important factors that warrant further investigation.

show abstract

“…Maternal serum IL-10 increased with further increase in pregnancy period. It has been indicated that Il-10 has a role in regulating placental development and programming (Roberts et al, 2003). Furthermore, the derived cytokine as IL-10 may be associated to normal human pregnancy and labor (Opsjłn et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-10, Mean Arterial Blood Pressure and Insulin Resistance in Normal Pregnancy

Jahromi¹,

Farjam²,

Davami³

et al. 2011

OnLine Journal of Biological Sciences

View full text Add to dashboard Cite

Problem statement:The purpose of this study was to investigate whether serum of Interleukin-10 (IL-10) Concentration change during normal pregnancy and, if so, to relate these changes corresponding alterations in insulin resistance and blood pressure. Approach: This cross sectional study was carried out on 86 healthy pregnant women including 26, 23 and 37 individuals in the 1st, 2nd and 3rd trimesters, respectively and in 21 healthy non pregnant women. Serum IL-10 concentration was measured by Enzyme Linked Immunosorbent Assay (ELISA) method. Insulin resistance value was calculated using the homeostasis model assessment, HOMA-IR. Results: Serum IL-10 concentration was found to be significantly higher in patients in all gestational age as compared non pregnant women. Il-10 level was significantly increased with increase in gestational age. Pregnant women exhibited higher score of HOMA IR compared non pregnant women, but there were no difference in this score between pregnant subjects in different gestational age. There were not significant correlation between IL-10 level with IR and blood pressure. Conclusion: The results of the study show maternal IL-10 level increase with further increase in gestational age and there is no significant correlation between IL-10 level with Mean Arterial blood Pressure (MAP) and IR.

show abstract

Altered Placental Development in Interleukin-10 Null Mutant Mice

Cited by 42 publications

References 27 publications

Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice

Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice

Maternal Immune Activation and Autism Spectrum Disorder: Interleukin-6 Signaling as a Key Mechanistic Pathway

Interleukin-10, Mean Arterial Blood Pressure and Insulin Resistance in Normal Pregnancy

Contact Info

Product

Resources

About