essay: Neurodevelopmental risk from vaccination during pregnancy: autism & schizophrenia

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essay: Neurodevelopmental risk from vaccination during

pregnancy: autism & schizophrenia

Neurodevelopmental risk from vaccination during pregnancy: autism &

schizophrenia

Binstock, Dec 31, 2009

ps: This post may be forwarded hither, yon, & beyond.

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

-Athill E et al.

University of South Florida

J Neuroimmunol. 2009 Dec 10;217(1-2):20-7. Epub 2009 Sep 18.

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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.

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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.

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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] 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

SE, Li J, Garbett K, Mirnics K, 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

Binstock, Sep 07, 2009

http://www.generationrescue.org/binstock/090907-vaccination-cytokines-schizophrenia.htm

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