BASIC SCIENCE: OBSTETRICS
Magnesium sulfate ameliorates maternal and fetal
inﬂammation in a rat model of maternal infection
Hima B. Tam Tam, MD; Oonagh Dowling, PhD; Xiangying Xue, MD;
Dawnette Lewis, MD, MPH; Burton Rochelson, MD; Christine N. Metz, PhD
Magnesium sulfate is proposed to have neuroprotective
effects in the offspring. We examined the effects of maternal magne-
sium sulfate administration on maternal and fetal inﬂammatory re-
sponses in a rat model of maternal infection.
Pregnant rats were injected with saline, Gram-negative
bacterial endotoxin lipopolysaccharide or lipopolysaccharide with magne-
sium sulfate (pre- and/or after lipopolysaccharide) to mimic infection. Ma-
ternal blood, amniotic ﬂuid, fetal blood, and fetal brains were collected 4
hours after lipopolysaccharide and assayed for tumor necrosis factor, inter-
leukin-6, monocyte chemoattractant protein-1, and growth-related onco-
gene-KC. In addition, the effect of magnesium sulfate on cytokine produc-
tion by an astrocytoma cell line was assessed.
Lipopolysaccharide administration induced tumor necrosis
factor, interleukin-6, monocyte chemoattractant protein-1, and
growth-related oncogene-KC expression in maternal and fetal compart-
ments. Maternal magnesium sulfate treatment signiﬁcantly attenuated
lipopolysaccharide-induced multiple proinﬂammatory mediator levels
in maternal and fetal compartments.
Antenatal magnesium sulfate administration signiﬁcantly
ameliorated maternal, fetal, and gestational tissue-associated inﬂamma-
tory responses in an experimental model of maternal infection.
Key words: chemokines, cytokines, fetal brain damage, GRO-KC,
magnesium sulfate, maternal infection, MCP-1, neuroprotection,
Cite this article as: Tam Tam HB, Dowling O, Xue X, et al. Magnesium sulfate ameliorates maternal and fetal inﬂammation in a rat model of maternal infection.
Am J Obstet Gynecol 2011;204:364.e1-8.
reterm birth is a major cause of peri-
natal morbidity and accounts for
approximately 70% of all perinatal mor-
Maternal infection, a major risk
factor for preterm labor,
with signiﬁcant neonatal morbidity, in-
cluding neurologic injury.
nal inﬂammatory response to infection
is characterized by the production of
proinﬂammatory mediators such as cy-
tokines and chemokines, which can lead
to tissue injury when produced in excess.
Lipopolysaccharide (LPS), the Gram
negative bacterial endotoxin, has been
used in laboratory animals to character-
ize the underlying pathogenesis of in-
to investigate infection-
associated fetal neuronal damage,
and to test various potential therapeutic
tration to pregnant laboratory animals
induces proinﬂammatory mediator pro-
duction in the maternal and fetal com-
partments. This model mimics the ele-
vated levels of cytokines and chemokines
(eg, tumor necrosis factor-alpha [TNF],
interleukin-6 [IL-6], monocyte che-
moattractant protein [MCP-1, CCL2])
observed in maternal and fetal compart-
ments during infection and/or preterm
Excessive and sus-
tained inﬂammatory mediator produc-
tion is proposed to activate the prosta-
glandin cascade leading to preterm birth,
a risk factor for neurologic damage.
In addition, fetal exposure to inﬂamma-
tory mediators is understood to be
linked to neurologic insults in the off-
spring, including long-term neurocogni-
tive dysfunction and cerebral palsy.
Several reports support the neuro-
protective effect of magnesium sulfate
) in the fetus. A randomized
clinical trial by Rouse and colleagues
showed a signiﬁcantly lower rate of cere-
bral palsy among infants born to women
at 24-31 weeks’ gestation who received
tocolysis for preterm labor. A re-
and the Cochrane
also supported this association.
has been used in ob-
stetrics for suppressing preterm labor, its
exact mechanism of action is unknown.
Research in our laboratory revealing that
attenuated cytokine produc-
tion by cultured endothelial cells high-
lights the antiinﬂammatory activity of
Additional in vivo studies
demonstrating exaggerated inﬂamma-
tory responses in Mg-deﬁcient animals
in the absence
further support the antiinﬂammatory ef-
fects of MgSO
From the Division of Maternal Fetal Medicine,
Department of Obstetrics and Gynecology
(Drs Tam Tam, Lewis, Rochelson); and The
Center for Immunology and Inﬂammation
and Merinoff Center for Patient-Oriented
Research (Drs Dowling, Xue, Metz), The
Feinstein Institute for Medical Research, North
Shore-LIJ Health System, Manhasset, NY.
Presented in abstract form and as an oral
presentation at the Annual Society of Maternal-
Fetal Medicine Meeting, Feb. 6, 2010.
Received Aug. 23, 2010; accepted Nov. 2,
Reprints not available from the authors.
The Oxenhorn Family and the Feinstein
Institute for Medical Research provided
Dr Dawnette Lewis is currently at Long Island
College Hospital, Brooklyn, NY.
© 2011 Mosby, Inc. All rights reserved.
APRIL 2011 American Journal of Obstetrics & Gynecology