Maternal Intrauterine Infection, Cytokines, and Brain Damage in the Preterm Newborn

Dammann, Olaf; Leviton, Alan

doi:10.1203/00006450-199707000-00001

Cited by 830 publications

(569 citation statements)

References 114 publications

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“…Indeed, in our population, 48.7% of deaths occurred in the first 5 d of life, largely due to respiratory causes, and respiratory distress syndrome was more common in the hypertensive than in the presumed infection/inflammation group (OR = 1.41, 95% CI 1.1-1.8, adjusted for GA, sex, and antenatal steroids). In recent years, great attention has been paid to the adverse effects of intrauterine infection, mainly chorioamnionitis, on neonatal lung and brain, and the association between antenatal infection and cerebral white matter damage has gained wide acceptance (17,18). Our findings corroborate the association between infection/inflammation and ultrasound-diagnosed cerebral lesions.…”

Section: Pregnancy Disorders and Neonatal Outcomesupporting

confidence: 80%

Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study

Gagliardi

Rusconi

Frè³

et al. 2013

Pediatr Res

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Section: Pregnancy Disorders and Neonatal Outcomesupporting

confidence: 80%

Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study

Gagliardi

Rusconi

Frè³

et al. 2013

Pediatr Res

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“…However, recent data indicate that other indices of inflammation/ infection such as cytokine levels may be elevated in schizophrenic and autistic blood and CSF samples. 43 Thus absence of gliosis alone should not be construed as absence of neuroimmunologic dysfunction. A recent report 44 demonstrated significant increases in density of HLA-DR+ microglia in temporal and frontal cortices of schizophrenics independent of the aging process, as well as a nonsignificant trend for increased astroglial numerical density in schizophrenic brains.…”

Section: Discussionmentioning

confidence: 99%

Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice

et al. 2002

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Epidemiological reports describe a strong association between prenatal human influenza viral infection and later development of schizophrenia. Postmodern human brain studies, however, indicate a lack of gliosis in schizophrenic brains presumably secondary to absence of glial cells during the second trimester viral infection in utero. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of glial fibrillary acidic protein (GFAP, an important marker of gliosis, neuron migration, and reactive injury) in developing brains of postnatal days 0, 14 and 35 mice. Determination of cellular GFAP immunoreactivity (IR) expressed as cell density in cortex and hippocampus of control and experimental brains showed increases in GFAP-positive density in exposed cortical (P = 0.03 day 14 vs control) and hippocampal cells (P = 0.035 day 14, P = 0.034 day 35). Similarly, ependymal cell layer GFAP-IR cell counts showed increases with increasing brain age from day 0, to days 14 and 35 in infected groups (P = 0.037, day 14) vs controls. The GFAP-positive cells in prenatally exposed brains showed 'hypertrophy' and more stellate morphology. These results implicate a significant role of prenatal human influenza viral infection on subsequent gliosis, which persists throughout brain development in mice from birth to adolescence.

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“…This implies either that LPS is not transported across the placenta and/or that the fetus has alternative mechanisms that block upregulation in TNF-␣ and IL-6 gene expression. Such mechanisms would be expected to be of benefit in sparing the developing fetus from sublethal effects of inflammatory cytokines, particularly the brain which is at risk of intraventricular hemorrhage and white matter damage elicited by endotoxin-induced cytokines during intrauterine infection (30,41). Our findings of differential cytokine content and synthesis in different compartments of the gestational tissues is consistent with a previous report on cytokine production after intrauterine infection in wild-type mice, where considerably more IL-1, IL-6, and TNF-␣ immunoactivity was detected in the uterus than the placenta, and fetal content was lower still (42).…”

Section: Discussionmentioning

confidence: 99%

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

Robertson

Skinner

Care

2006

The Journal of Immunology

173

138

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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.

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Maternal Intrauterine Infection, Cytokines, and Brain Damage in the Preterm Newborn

Cited by 830 publications

References 114 publications

Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study

Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study

Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice

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

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