Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
December 31, 2009
An increasing amount of data indicates that when a pregnant woman is
vaccinated, cytokines induced by the vaccination increase the
likelihood that her embryo or fetus will experience atypical brain
development.
For instance, " Maternal immune activation (MIA) can affect fetal brain
development and thus behavior of young and adult offspring. Reports
have shown that increased Interleukin-6 (IL-6) in the maternal serum
plays a key role in altering fetal brain development, and may impair
social behaviors in the offspring." (1)
Relevant is the fact that influenza vaccination increases IL-6 (2).
Indeed, commenting on the IL-6 finding (1), University of Minnesota
neuroscientist S. Hossein Fatemi, M.D., Ph.D., described the autism
significance of dysregulation of maternal immunity (3).
Importantly and free online, a detailed but readable elaboration of
maternal inflammation and adverse sequelae is presented by M.I.N.D.
Institute's Isaac N. Pessah, Ph.D., and colleagues (section V in cite
4). Given findings summarized in that part of the Pessah et al review
(4), oft-repeated admonitions to vaccinate pregnant women - and thus
recommendations and policies to induce transient elevations of
interleukin-6 and other cytokines - may be properly categorized as an
insanity of modernity.
When reading section V of Pessah et al (4), a further parallel to
vaccinations merits attention. In many experiments maternal
inflammation was induced by a non-pathogenic agent that stimulated
maternal cytokines in ways akin to pathogen-induced cytokines (4) and
vaccination-induced cytokines (2). In other words, effects the
cytokines induced in the pregant female may be as important or even
more important than the pathogen itself.
A (free online) study published in 2007 states, "The identification of IL-6 as a key intermediary should
aid in the molecular dissection of the pathways whereby [maternal
immune activation] MIA alters fetal brain development, which can shed
new light on the pathophysiological mechanisms that predispose to
schizophrenia and autism." (5; see also 6-7)
Needless to say, Hell will have thoroughly frozen over long before
high-ranking personnel of the Institute of Medicine, Advisory Committee
for Immunization Practices, the FDA, American Academy of Pediatrics, or
the American Medical Association move toward vaccine safety by revising
vaccination policies in ways consistent with the findings summarized
herein (1-7; see also 8).
References:
1. Flavonoids, a prenatal prophylaxis via
targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated
autism
Parker-Athill E et al.
University of South Florida
J Neuroimmunol. 2009 Dec 10;217(1-2):20-7. Epub 2009 Sep 18.
$ http://www.jni-journal.com/article/S0165-5728%2809%2900316-6/abstract
Maternal immune activation (MIA) can affect fetal brain development and
thus behavior of young and adult offspring. Reports have shown that
increased Interleukin-6 (IL-6) in the maternal serum plays a key role
in altering fetal brain development, and may impair social behaviors in
the offspring. Interestingly, these effects could be attenuated by
blocking IL-6. The current study investigated the effects of luteolin,
a citrus bioflavonoid, and its structural analog, diosmin, on IL-6
induced JAK2/STAT3 (Janus tyrosine kinase-2/signal transducer and
activator of transcription-3) phosphorylation and signaling as well as
behavioral phenotypes of MIA offspring. Luteolin and diosmin inhibited
neuronal JAK2/STAT3 phosphorylation both in vitro and in vivo following
IL-6 challenge as well as significantly diminishing behavioral deficits
in social interaction. Importantly, our results showed that diosmin
(10mg/kgday) was able to block the STAT3 signal pathway; significantly
opposing MIA-induced abnormal behavior and neuropathological
abnormalities in MIA/adult offspring. Diosmin's molecular inhibition of
JAK2/STAT3 pathway may underlie the attenuation of abnormal social
interaction in IL-6/MIA adult offspring.
2. Effect of influenza vaccine on markers
of inflammation and lipid profile
Tsai MY et al.
University of Minnesota
J Lab Clin Med. 2005 Jun;145(6):323-7.
$ http://www.journals.elsevierhealth.com/periodicals/ymlc/article/S0022-2143%2805%2900125-3/abstract
Despite wide use of the influenza vaccine, relatively little is known
about its effect on the measurement of inflammatory markers. Because
inflammatory markers such as C-reactive protein (CRP) are increasingly
being used in conjunction with lipids for the clinical assessment of
cardiovascular disease and in epidemiologic studies, we evaluated the
effect of influenza vaccination on markers of inflammation and plasma
lipid concentrations. We drew blood from 22 healthy individuals 1 to 6
hours before they were given an influenza vaccination and 1, 3, and 7
days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte
chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble
receptor alpha, and serum amyloid A were measured, and differences in
mean concentrations of absolute and normalized values on days 1, 3, and
7 were compared with mean baseline values. There
was a significant increase in mean IL-6 (P < .01 absolute
values, P < .001 normalized values) on day 1
after receiving the influenza vaccine. The mean increases in
normalized high sensitivity CRP values were significant on day 1 (P
< .01) and day 3 (P = .05), whereas the mean increase in normalized
serum amyloid A was significant only on day 1 (P < .05). No
significant changes were seen in mean concentrations of IL-2 soluble
receptor alpha, monocyte chemotactic protein-1, or tumor necrosis
factor-alpha. Of the lipids, significant decreases in mean
concentrations of normalized triglyceride values were seen on days 1 (P
< .05), 3 (P < .001), and 7 (P < .05) after vaccination. Our
findings show that the influenza vaccination causes transient changes
in select markers of inflammation and lipids. Consequently, clinical
and epidemiologic interpretation of the biomarkers affected should take
into account the possible effects of influenza vaccination.
3. Multiple pathways in prevention of
immune-mediated brain disorders: Implications for the prevention of
autism
Fatemi SH.
J Neuroimmunol. 2009 Dec 10;217(1-2):8-9. Epub 2009 Oct 14.
$ http://www.jni-journal.com/article/S0165-5728%2809%2900357-9/abstract
4. V. The Impacts of Maternal Immune
Challenge on the Fetal Brain and the Pathological Consequences on
Behavior
[a summary of findings by]
Benjamin K. Yee, Urs Meyer, and Joram Feldon, Laboratory of Behavioural
Neurobiology, ETH Zurich, Switzerland
in: Immunologic and
neurodevelopmental susceptibilities of autism
Pessah IN, Seegal RF, Lein PJ, LaSalle J, Yee BK, Van De Water J,
Berman RF.
Neurotoxicology. 2008 May;29(3):532-45.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475601/pdf/nihms55471.pdf
Symposium 5 focused on research approaches that are aimed at
understanding common patterns of immunological and neurological
dysfunction contributing to neurodevelopmental disorders such as autism
and ADHD. The session focused on genetic, epigenetic, and environmental
factors that might act in concert to influence autism risk, severity
and co-morbidities, and immunological and neurobiological targets as
etiologic contributors. The immune system of children at risk of autism
may be therefore especially susceptible to psychological stressors,
exposure to chemical triggers, and infectious agents. Identifying early
biomarkers of risk provides tangible approaches toward designing
studies in animals and humans that yield a better understanding of
environmental risk factors, and can help identify rational intervention
strategies to mitigate these risks.
5. Maternal immune activation alters
fetal brain development through interleukin-6
Smith SE, Li J, Garbett K, Mirnics K, Patterson PH.
California Institute of Technology
J Neurosci. 2007 Oct 3;27(40):10695-702.
http://www.jneurosci.org/cgi/content/full/27/40/10695
Schizophrenia and autism are thought to result from the interaction
between a susceptibility genotype and environmental risk factors. The
offspring of women who experience infection while pregnant have an
increased risk for these disorders. Maternal immune activation (MIA) in
pregnant rodents produces offspring with abnormalities in behavior,
histology, and gene expression that are reminiscent of schizophrenia
and autism, making MIA a useful model of the disorders. However, the
mechanism by which MIA causes long-term behavioral deficits in the
offspring is unknown. Here we show that the cytokine interleukin-6
(IL-6) is critical for mediating the behavioral and transcriptional
changes in the offspring. A single maternal injection of IL-6 on day
12.5 of mouse pregnancy causes prepulse inhibition (PPI) and latent
inhibition (LI) deficits in the adult offspring. Moreover,
coadministration of an anti-IL-6 antibody in the poly(I:C) model of MIA
prevents the PPI, LI, and exploratory and social deficits caused by
poly(I:C) and normalizes the associated changes in gene expression in
the brains of adult offspring. Finally, MIA in IL-6 knock-out mice does
not result in several of the behavioral changes seen in the offspring
of wild-type mice after MIA. The identification of IL-6 as a key
intermediary should aid in the molecular dissection of the pathways
whereby MIA alters fetal brain development, which can shed new light on
the pathophysiological mechanisms that predispose to schizophrenia and
autism.
6. The effects of maternal
inflammation on neuronal development: possible
mechanisms
Jonakait GM.
New Jersey Institute of Technology
Int J Dev Neurosci. 2007 Nov;25(7):415-25. Epub 2007 Sep 14.
That maternal inflammation adversely affects fetal brain development is
well established. Less well understood are the mechanisms that account
for neurodevelopmental disorders arising from maternal inflammation.
This review seeks to begin an examination of possible sites and
mechanisms of action whereby inflammatory cytokines - produced by the
mother or by the fetal brain - could impact the developing fetus. We
focus first on the placenta where cytokines maintain the immunological
environment that prevents maternal rejection of the fetus. Following a
brief examination of placental transfer of maternal cytokines, the
focus turns on embryonic microglia, early and ubiquitous residents of
the developing brain. Finally, a more intense examination of
interleukin-6 (IL-6) and bone morphogenetic proteins (BMPs) provides
examples of glial- or maternal-derived cytokines that are known to have
profound effects on developing systems and that could, if dysregulated,
have undesirable consequences for brain development.
7. The
role of pro-inflammatory factors in mediating the effects on the fetus
of prenatal undernutrition: implications for
schizophrenia
Shen Q et al.
Schizophr Res. 2008 Feb;99(1-3):48-55. Epub 2007 Dec 11.
Exposure to prenatal undernutrition or malnutrition increases the risk
of schizophrenia, although little is known about the mechanism.
Pro-inflammatory factors are critical in brain development, and are
believed to play an important role in neurodevelopmental disorders
associated with prenatal exposure to infection, including
schizophrenia. However it is not known whether pro-inflammatory factors
also mediate the effects on the fetus of prenatal malnutrition or
undernutrition. In this study, we established a new prenatal
undernourished rat model induced by maternal exposure to a diet
restricted to 50% of the low (6%) protein diet (RLP50). We observed the
disappearance of maternal nest-building behavior in the RLP50 dams,
increased levels of TNFA and IL6 in the placentas (P<0.001; P=0.879,
respectively) and fetal livers (P<0.001; P<0.05, respectively),
and a decrease in the fetal brains (P<0.05; P<0.01,
respectively). Our results are similar to previous studies of maternal
infection, which implies that a common pathway mediated by
pro-inflammatory factors may contribute to the brain development,
consequently increasing the risk of schizophrenia and other psychiatric
diseases programmed by varied maternal adversities. We also provide a
new prenatal undernourished model for researching prenatal problems,
which differs from previous malnourished model in terms of the maternal
behavior of dams and of observed pro-inflammatory factor levels in
fetal tissues.
8. Vaccination-induced cytokines:
schizophrenia & developmental disabilities
Teresa Binstock, Sep 07, 2009
http://www.ravenintellections.com/gre/vax-cytokines-schizophrenia-risk.htm
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