|
Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
September 07, 2009
Introduction: An increasing body of peer-reviewed evidence indicates that
when a woman is pregnant, transiently elevated cytokines can induce
atypical brain development in her embryo or fetus. Illnesses and
vaccinations induce
elevation of cytokines, and these elevations can be heightened in
individuals with alleles of genes related to immune responses. An
implication of citations supporting these relationships is
that vaccinating pregnant women is likely to induce cognitive and
behavioral pathologies in as least some children whose mothers were
vaccinated while the child was in utero. Schizophrenia and developmental disabilities are pathologies that may ensue.
Stacy Bilbo & Jaclyn Schwarz have written an important
review, "Early-life programming of later-life brain and
behavior: a critical role for the immune system".
The peer-reviewed
paper is free online (1) and is especially relevant amid
recommendations that pregnant women be vaccinated for
seasonal influenza and for lab-related H1N1 swine flu. Evidence discussed by Bilbo & Schwarz prompts a question: Will
vaccinating pregnant women induce cytokine
elevations likely to damage the embryonic or fetal brain of at least
some women?
Published studies indicate that (i) transiently elevated
cytokines
can alter brain development in utero, and (ii) illnesses and
vaccinations cause
elevated levels of various cytokines. These two factors indicate that
at least some women will have children who develop untoward traits
induced in utero as a result of their mother's having been vaccinated
during pregnancy.
Because cytokines are complex (2), only two will be considered
here, interleukin-6 and interleukin-1beta (IL-6, IL-1b).
Interleukin-6 and interleukin-1beta are among the cytokines elevated by
influenza vaccination (3-6). These elevations parallel those induced by
influenza itself.
Current recommendations for a seasonal-influenza vaccination
accompanied by one or two swine flu (H1N1) vaccinations need be
considered in regard to the following: "There are several reports in
humans that influenza infection
induces cytokine production by the maternal immune system, the fetal
immune system, and the placenta..., and each has been
linked to increased risk of schizophrenia in the offspring..." (1,
citing 7-9; see also 10).
In addition to increased risk for schizophrenia, maternal cytokines
(especially IL-1b) induced by vaccinating pregnant women may alter the
subsequent child's cognitive skills related to memory (reviewed in 1).
As one researcher summarizes, "Prenatal exposure to infection appears
to increase the risk of schizophrenia and other neurodevelopmental
disorders." (8)
Clarification: This essay is not asserting that ALL pregnant women who
receive injections of anti-influenza vaccine and/or injections of
anti-H1N1 vaccine (many brands of which will contain thimerosal and/or
squalene) will give birth to a child who later develops schizophrenia
or a developmental disorder. Instead, the evidence cited in this essay
indicates that, among women who receive one or more vaccinations during
pregnancy and thereby experience cytokines elevations that affect her
fetus, there will be an increased risk for having a child who, some years later, will develop
schizophrenia or a developmental disability.
A pregnant woman's options are discomforting. If she develops swine flu
or seasonal influenza, she may induce cytokine elevations which
adversely affect her fetus. If she allows herself to be vaccinated
during pregnancy, her body's reaction will include cytokine elevations
which may adversely affect brain development of some fetuses - and do
in ways that become apparent only during early childhood, adolescence,
or young adulthood (reviewed in 1).
For individuals with a technical bent, the Bilbo and Schwarz review is
recommended (1). In short, it summarizes known effects of maternal
elevations of interleukin-6 and interleukin-1beta. Additionally, the
review elaborates increasing evidence supporting the "two hit"
hypothesis, wherein an in utero event such as transiently elevated
cytokines induces fetal changes which potentiate more serious sequelae
pursuant to postnatal events in the offspring (eg, illness).
Media reports tell us that the safety of swine flu vaccinations will be
evaluated. However, some reports have mentioned that thimerosal or
squalene may not be present in the vaccines tested early, thus raising
questions about "safety" pronouncements we'll be hearing. Furthermore, if the influenza or swine flu
vaccinations' adverse events include developmental disabilities and
schizophrenia, which will occur some years after the vaccinating of
pregnant women, the monitoring of those adverse events will be impossible in the months ahead.
More generally, we ask if vaccinologists are prone to hubris?
Their willingness to inject thimerosal and squalene (MF59) despite
voluminous evidence of harm caused by those substances appalls. An
autism parent raises an important issue (11), are many and perhaps most
vaccinologists rushing forth while ignoring advances in immunology,
while ignoring findings which indicate why some individuals are more
likely to experience adverse effects from vaccinations, especially
during pregnancy?
Postscript: This essay calls attention to adverse effects induced by cytokines elevated by vaccinations and only briefly mentions adverse effects induced by thimerosal (12) and by squalene (13). Not considered is the additive or synergistic effects of the three components: cytokine elevations, squalene, and thimerosal.
References:
1. Early-life programming of later-life
brain and behavior: a critical role for the immune system
Bilbo SD, Schwarz JM.
Frontiers in Behavioral Neuroscience 2009 3(14)1-14.
http://frontiersin.org/behavioralneuroscience/paper/10.3389/neuro.08/014.2009/pdf/
2. Cytokine
http://en.wikipedia.org/wiki/Cytokine
3. Effect of influenza vaccine on markers
of inflammation and lipid
profile
Tsai MY et al.
J Lab Clin Med. 2005 Jun;145(6):323-7.
Laboratory of Medicine and Pathology, University of Minnesota
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.
4. Genetic predisposition of the
interleukin-6 response to
inflammation: implications for a variety of major diseases?
Bennermo M, Held C, Stemme S, Ericsson CG, Silveira A, Green F,
Tornvall P.
Department of Medicine, Danderyd University Hospital, Stockholm, Sweden.
Clin Chem. 2004 Nov;50(11):2136-40.
{free online}
http://www.clinchem.org/cgi/content/full/50/11/2136
BACKGROUND: A single-nucleotide polymorphism (SNP) in the promoter
region of the interleukin-6 (IL-6) gene at position -174 (G>C) has
been reported to be associated with a variety of major diseases, such
as Alzheimer disease, atherosclerosis, and cardiovascular disease,
cancer, non-insulin-dependent diabetes mellitus, osteoporosis, sepsis,
and systemic-onset juvenile chronic arthritis. However, authors of
previous in vitro and in vivo studies have reported conflicting results
regarding the functionality of this polymorphism. We therefore aimed to
clarify the role of the -174 SNP for the induction of IL-6 in vivo.
METHODS: We vaccinated 20 and 18 healthy individuals homozygous for the
-174 C and G alleles, respectively, with 1 mL of Salmonella typhii
vaccine. IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha)
were measured in the blood at baseline and up to 24 h after
vaccination. RESULTS: Individuals with the G genotype had significantly
higher plasma IL-6 values at 6, 8, and 10 h after vaccination than did
individuals with the C genotype (P <0.005). There were no
differences between the two genotypes regarding serum concentrations of
IL-1beta and TNF-alpha before or after vaccination. CONCLUSIONS: The
-174 G>C SNP in the promoter region of the IL-6 gene is functional
in vivo with an increased inflammatory response associated with the G
allele. Considering the central role of IL-6 in a variety of major
diseases, the present finding might be of major relevance.
excerpt: Interleukin 6 (IL-6) is a key proinflammatory cytokine produced
by many different cells, including leukocytes, adipocytes,
endothelial cells, fibroblasts, and myocytes. IL-6
regulates production of adhesion molecules and induces
secretion of monocyte chemotactic protein, an important
mediator of release of other cytokines, such as tumor
necrosis factor- (TNF-)
and interleukin-1ß (IL-1ß), that subsequently amplify the
inflammatory reaction(1).
excerpt: We chose vaccination as a stimulus because it has
been shown to increase plasma IL-6 concentrations and to
have a detrimental effect on endothelial function(24).
excerpt: The main finding of the present study was that healthy
individuals homozygous for the G allele of the –174 SNP
located in the promoter region of the IL-6 gene had a
stronger inflammatory IL-6 response to vaccination against S.
typhii compared with individuals homozygous for the C
allele.
excerpt: Previous in vitro studies (2)(20)
have shown that the G allele of the –174 SNP was associated
with increased transcription when stimulated by endotoxin
and IL-1ß.
excerpt: ...the increased IL-6 response associated with the
G allele might be harmful in the development of chronic
diseases, such as NIDDM and atherosclerosis, by increasing the
inflammatory stress when challenged repeatedly by minor stimuli.
For example, insulin resistance has been associated with
the G allele (14),
and the G allele has been reported more frequently among
Pima Indians and Caucasians with NIDDM (13).
5. Urinary tract diseases revealed after
DTP vaccination in infants and
young children: cytokine irregularities and down-regulation of
cytochrome P-450 enzymes induced by the vaccine may uncover latent
diseases in genetically predisposed subjects.
Prandota J.
Am J Ther. 2004 Sep-Oct;11(5):344-53.
Prophylactic vaccinations may sometimes shorten the incubation period
of some illnesses and/or convert a latent infection/inflammation into a
clinically apparent disease. Cytokines play a major role in mediating
the inflammatory process in various clinical entities and represent a
potential source of tissue damage if their production is not
sufficiently well controlled. It seems that irregularities in
production of proinflammatory cytokines may be responsible for the
abnormalities associated with full-blown clinical symptoms of various
urinary tract diseases observed after DTP vaccination in 13 infants and
young children hospitalized over the past 24 years. On admission, upper
respiratory tract diseases, atopic dermatitis, and/or latent urinary
tract infection/inflammation were found in these children. It is
suggested that the whole-cell pertussis present in DTP vaccine, acting
as an excessive stimulus in these patients, produced symptoms
reminiscent of biologic responses to circulating proinflammatory
monokines such as IL-1beta, TNF-alpha, and IL-6 because earlier it was
reported that in vitro the whole-cell vaccine induced significantly
more such cytokine production than did the acellular pertussis or
diphtheria-tetanus-only vaccine. Analysis of the cellular immune
disturbances previously reported in urinary tract
infection/inflammation (increased serum and/or urinary IL-1alpha, IL-1
receptor antagonist, IL-6 and IL-8), steroid-sensitive nephrotic
syndrome (increased IL-2, IFN-gamma, TNF-alpha, and decreased or
increased IL-4, depending on the cells studied), and atopic dermatitis
(decreased IFN-gamma and increased IL-4 production), may suggest that
similar subclinical chronic cytokine-mediated abnormalities produced in
the course of latent diseases revealed in our patients, combined with
those caused by DTP vaccination stimulus, were responsible for the
pathomechanism of these clinical entities. This speculation is in
agreement with the reports on the long-lasting induction of cytokine
release and down-regulation of hepatic cytochrome P-450 isoenzyme
activities after administration of DTP vaccine to mice and may be
supported by the fact that TH1 phenotype is associated with the
up-regulation of intercellular adhesion molecule-1 and RANTES, whereas
TH2 phenotype is associated with the up-regulation of the vascular cell
adhesion molecule and P-selectin, which are key players in the
migration into inflamed tissues and localization of lymphocytes and
other allergic effector and inflammatory cells. Because several
inflammatory cytokines down-regulate gene expression of major
cytochrome P-450 and/or other enzymes with the specific effects on mRNA
levels, protein expression, and enzyme activity, thus affecting the
metabolism of several endogenous lipophilic substances such as
steroids, lipid-soluble vitamins, prostaglandins, leukotrienes,
thromboxanes, and exogenous substances, their irregularities in the
body may eventually lead to the flare of latent diseases in some
predisposed subjects. Also, interleukin genetic polymorphisms,
especially the constellation of TNF-alpha and IL-6 genetic variants,
might predispose some infants with infection to a more than usually
intense inflammatory response in the kidneys after vaccination. It
seems that the aforementioned pathomechanism may also be responsible
for some cases of sudden infant death syndrome, which is often preceded
by infection/inflammation.
6. IL-1beta gene polymorphisms influence
hepatitis B vaccination.
Yucesoy B et al.
Vaccine. 2002 Aug 19;20(25-26):3193-6.
Considerable variability exists in the vaccine response to hepatitis B
with 5-10% of healthy young adults demonstrating no or inadequate
responses following a standard vaccination schedule. As the
interleukin-1beta (IL-1beta) cytokine has been shown to be important in
the development of immune responses, we determined whether vaccine
efficacy is influenced by genetic polymorphisms associated with
IL-1beta expression. Ninety-two healthy individuals who were negative
for antibodies to hepatitis B antigen (anti-HBs) were vaccinated
against hepatitis B according to a standardized schedule. At selected
times, antibody titers and lymphoproliferative capacity to hepatitis B
surface antigen (HBsAg) were determined. DNA genotyping for IL-1beta
polymorphisms using a polymerase chain reaction (PCR)-restriction
fragment length polymorphism (RFLP) technique demonstrated that both
the anti-HBs titer and the T-cell lymphoproliferative response to HBsAg
are significantly increased in individuals possessing the IL-1beta
(+3953) minor allelic variant. Copyright 2002 Elsevier Science Ltd.
7. The relationship of amniotic fluid
cytokines and preterm delivery,
amniotic fluid infection, histologic chorioamnionitis, and chorioamnion
infection
Hillier SL et al.
Obstet Gynecol 1993 81:941-8.
OBJECTIVE: To assess the association between cytokines in the amniotic
fluid (AF) and preterm delivery, the isolation of bacteria from the AF
or chorioamnion, and histologic chorioamnionitis. METHODS: Fifty
afebrile women with intact membranes in preterm labor at or before 34
weeks' gestation underwent amniocentesis. Cytokine levels were measured
in AF, and cultures were performed. Placentas were cultured and
examined histologically. RESULTS: Thirty-two (64%) of the 50 patients
delivered at or before 34 weeks' gestation. Delivery at or before 34
weeks, compared with delivery after 34 weeks, was related to increased
levels of interleukin-6 (IL-6) (88 versus 12%; P < .001),
interleukin-1 (IL-1) alpha (50 versus 6%; P = .004), IL-1 beta (42
versus 0%; P = .002), and prostaglandin (PG) E2 (66 versus 22%; P =
.008). Bacteria were recovered from the AF of nine (18%) of the 50
patients. All of the cytokines with increased levels, plus tumor
necrosis factor (TNF)-alpha, were related to bacteria in the AF.
Increased IL-6, IL-1 alpha, IL-1 beta, TNF-alpha, and PGE2 were also
associated with histologic chorioamnionitis among women who delivered
within 1 week of amniocentesis. Elevated cytokine levels were not
related to chorioamnion infection. CONCLUSIONS: Elevated AF cytokines
and PGE2 predicted delivery before 34 weeks' gestation and delivery
within 7 days of the amniocentesis, as well as AF infection and
histologic chorioamnionitis. These findings support the hypothesis that
infection is one cause of preterm delivery, operating via a mechanism
involving induction of cytokine production.
8. Prenatal exposure to maternal infection
alters cytokine expression
in the placenta, amniotic fluid, and fetal brain
Urakubo A et al.
Schizophren Res 2001 47:27-36.
Prenatal exposure to infection appears to increase the risk of
schizophrenia and other neurodevelopmental disorders. We have
hypothesized that cytokines, generated in response to maternal
infection, play a key mechanistic role in this association. E16 timed
pregnancy rats were injected i.p. with Escherichia coli
lipopolysaccharide (LPS) to model prenatal exposure to infection.
Placenta, amniotic fluid and fetal brains were collected 2 and 8h after
LPS exposure. There was a significant treatment effect of low-dose
(0.5mg/kg) LPS on placenta cytokine levels, with significant increases
of interleukin (IL)-1beta (P<0.0001), IL-6 (P<0.0001), and tumor
necrosis factor-alpha (TNF-alpha) (P=0.0001) over the 2 and 8h time
course. In amniotic fluid, there was a significant effect of treatment
on IL-6 levels (P=0.0006). Two hours after maternal administration of
high-dose (2.5mg/kg) LPS, there were significant elevations of placenta
IL-6 (P<0.0001), TNF-alpha (P<0.0001), a significant increase of
TNF-alpha in amniotic fluid (P=0.008), and a small but significant
decrease in TNF-alpha (P=0.035) in fetal brain. Maternal exposure to
infection alters pro-inflammatory cytokine levels in the fetal
environment, which may have a significant impact on the developing
brain.
9. Serologic evidence of prenatal
influenza in the etiology of
schizophrenia
Brown AS et al.
Arch Gen Psychiatry 2004 61:774-80.
{free online}
http://archpsyc.ama-assn.org/cgi/content/full/61/8/774
CONTEXT: Some, but not all, previous studies suggest that prenatal
influenza exposure increases the risk of schizophrenia. These studies
used dates of influenza epidemics and maternal recall of infection to
define influenza exposure, suggesting that discrepant findings may have
resulted from exposure misclassification. OBJECTIVE: To examine whether
serologically documented prenatal exposure to influenza increases the
risk of schizophrenia. DESIGN: Nested case-control study of a large
birth cohort, born from 1959 through 1966, and followed up for
psychiatric disorders 30 to 38 years later. SETTING: Population-based
birth cohort. PARTICIPANTS: Cases were 64 birth cohort members
diagnosed as having schizophrenia spectrum disorders (mostly
schizophrenia and schizoaffective disorder). Controls were 125 members
of the birth cohort, had not been diagnosed as having a schizophrenia
spectrum or major affective disorder, and were matched to cases on date
of birth, sex, length of time in the cohort, and availability of
maternal serum. MAIN OUTCOME MEASURES: Archived maternal serum was
assayed for influenza antibody in pregnancies giving rise to offspring
with schizophrenia and matched control offspring. RESULTS: The risk of
schizophrenia was increased 7-fold for influenza exposure during the
first trimester. There was no increased risk of schizophrenia with
influenza during the second or third trimester. With the use of a
broader gestational period of influenza exposure-early to
midpregnancy-the risk of schizophrenia was increased 3-fold. The
findings persisted after adjustment for potential confounders.
CONCLUSIONS: These findings represent the first serologic evidence that
prenatal influenza plays a role in schizophrenia. If confirmed, the
results may have implications for the prevention of schizophrenia and
for unraveling pathogenic mechanisms of the disorder.
10. Prenatal infection as a risk factor
for schizophrenia
Brown AS.
College of Physicians and Surgeons of Columbia University, NY State
Psychiatric Institute
Schizophr Bull. 2006 Apr;32(2):200-2
{free online}
http://schizophreniabulletin.oxfordjournals.org/cgi/content/full/32/2/200
Accumulating evidence suggests that prenatal exposure to infection
contributes to the etiology of schizophrenia. This line of
investigation has been advanced by birth cohort studies that utilize
prospectively acquired data from serologic assays for infectious and
immune biomarkers. These investigations have provided further support
for this hypothesis and permitted the investigation of new infectious
pathogens in relation to schizophrenia risk. Prenatal infections that
have been associated with schizophrenia include rubella, influenza, and
toxoplasmosis. Maternal cytokines, including interleukin-8, are also
significantly increased in pregnancies giving rise to schizophrenia
cases. Although replication of these findings is required, this body of
work may ultimately have important implications for the prevention of
schizophrenia, the elaboration of pathogenic mechanisms in this
disorder, and investigations of gene-environment interactions.
11. The “New Class” of Helper T Cells or
Things We Did Not Know Just Five Years Ago
Jack Russell, 06 September 2009
http://thelenseofautism.blogspot.com/2009/09/new-class-of-helper-t-cells-or-things.html
12. Autism, mercury, other toxic metals, & glutathione
Teresa Binstock, Aug 12, 2009.
http://www.generationrescue.org/binstock/090812-autism-toxic-metals-glutathione.htm
13. Lancet recommends caution for H1N1
vaccinations; ajduvants merit concern
Teresa Binstock, Aug 09, 2009
http://www.generationrescue.org/binstock/090809-Lancet-caution-H1N1-vaccination.htm
Back to Index |
