MMR's live viruses,
interferon gamma, and blood-brain barrier permeability
Researcher in Developmental & Behavioral Neuroanatomy
May 31, 2009
Introduction: MMR induces an extended pulse of interferon gamma
(IFNg), which increases permeability of the blood-brain barrier (BBB). An
inference is that more mercury will enter the brain when a toddler is injected
with the both the MMR and a thimerosal-containing vaccine during the same
vaccination incident. The mercury-into-brain effect is likely to be increased
because viral infections increase BBB permeability. Furthermore, the MMR induces
increases NK activity, but a large subgroup of autistic children has suboptimal
NK cytoxicity, which suggests that some children may have atypical and
suboptimal NK activity pursuant to live viruses injected during MMR incidents.
The findings summarized here call attention to plausible mechanisms by which
some children regress into autism or other autism-spectrum disorders subsequent
to vaccinations, especially after vaccination incidents wherein multiple
vaccines were injected at virtually the same time.
Here are some quotes, citations, and abstracts in support of these concerns.
"The protective effect of the BBB is... lost during bacterial and viral
"TNF-alpha, IL-1beta, interferon gamma (IFN-gamma), or lipopolysaccharide
(LPS)"... increased "the permeability of the tight junctions" of BBB endothelial
Regarding MMR, "Interferon-gamma was the principal cytokine produced after
primary measles immunization" (3), thus the MMR's pulse of interferon gamma (IFNg)
is likely to increase BBB permeability.
"45% of a subgroup of children with autism suffers from low NK cell activity"
Regarding MMR, "NK cells increased after immunization" (3), but NK activity
reduced by the MMR has been described (5), and a large subgroup of autistic
children has low NK cytotoxicity (5). These several findings suggest that
autistic children may be more inclined towards reduced NK activity after MMR
Inferences from these 5 studies prompt concerns. For instance,
a) Given that IFNg increases BBB permeability (2) and the MMR induces an
extended pulse of IFNg (3), would simultaneous injections of MMR and a
thimerosal-containing vaccine increase the amount of mercury that enters the
b) Given that the MMR contains live viruses, and given that viruses increase BBB
permeability (2), would simultaneous injections of MMR and a thimerosal-containing
vaccine increase the amount of mercury that enters the human brain?
c) Given that a large subgroup of autistic children has reduced effectiveness of
natural killer (NK) cells (4), and given that the MMR in healthy children causes
an increase in NK activity (3), would children having impaired NK function (5)
have atypical and suboptimal responses to MMR-related injections of live
1: Blood brain barrier and infection.
Med Sci Monit. 2000 Nov-Dec;6(6):1213-22.
The blood brain barrier (BBB) is a highly dynamic structure and consists of
endothelial cells, which are characterized by the presence of tight junctions
and relative lack of endocytic vesicles. The tight junctions are reinforced by
the foot processes of the astrocytes. The BBB functions through these
specialised structures, to maintain the environment of the brain in a steady
state by regulating the influx and efflux of substances. The protective effect
of the BBB is however, lost during bacterial and viral infections. The primary
mechanism operative are an increase in the permeability of the BBB and/or direct
invasion of the brain by microorganisms. Since the BBB is relatively impermeable
to chemotherapeutic agents the treatment of CNS infections is difficult. This
paper aims to examine the various mechanisms by which infection spreads to the
brain, and suggest measures for successful drug delivery into the brain during
2: Cytokines, nitric oxide, and cGMP modulate the permeability of an in vitro
model of the human blood-brain barrier.
Wong D, Dorovini-Zis K, Vincent SR.
Exp Neurol. 2004 Dec;190(2):446-55.
The endothelial cells (EC) of the microvasculature in the brain form the
anatomical basis of the blood-brain barrier (BBB). In the present study, the
effects of agents that modify the permeability of a well-established in vitro
model of the human BBB were studied. The monolayers formed by confluent human
brain microvessel endothelial cell (HBMEC) cultures are impermeable to the
macromolecule tracer horseradish peroxidase (HRP) and have high electrical
resistance. Exposure of HBMEC to various cytokines including TNF-alpha,
IL-1beta, interferon gamma (IFN-gamma), or lipopolysaccharide (LPS) decreased
transendothelial electrical resistance (TEER) mainly by increasing the
permeability of the tight junctions. Primary cultures of HBMEC express
endothelial nitric oxide synthase (eNOS) and produce low levels of NO. Treatment
with the NO donors sodium nitroprusside (SNP) and DETA NONOate or the cGMP
agonist 8-Br-cGMP significantly increased monolayer resistance. Conversely,
inhibition of soluble guanylyl cyclase with ODQ rapidly decreased the
resistance, and pretreatment of HBMEC with Rp-8-CPT-cGMPS, an inhibitor of cGMP-dependent
protein kinase, partially prevented the 8-Br-cGMP-induced increase in
resistance. Furthermore, NO donors and 8-Br-cGMP could also reverse the
increased permeability of the monolayers induced by IL-1beta, IFN-gamma, and
LPS. These results indicate that NO can decrease the permeability of the human
BBB through a mechanism at least partly dependent on cGMP production and cGMP-dependent
protein kinase activation.
3. Kinetics of immunologic responses after primary MMR vaccination.
Pabst HF et al.
Vaccine. 1997 Jan;15(1):10-4.
To study the kinetics of humoral as well as cellular immunity to measles and to
test for associated immunosuppression 124 12 month old children were studied
twice, before routine MMR and either 14, 22, 30, or 38 days after vaccination.
Plaque reduction neutralization (PRN) titres were determined at these time
points and lymphocytes were evaluated to identify changes in proportions of
phenotype, their capacity to generate cytokines and to respond to blast
transformation (BT) to measles hemagglutinin (HA), tetanus toxoid and Candida
antigen. The PRN titre and BT to HA plateaued at 30 days and CD8+ and NK cells
increased after immunization. Interleukin 2, 4, and 10 showed no significant
changes. There was mild suppression of BT at 14 and 22 days post-immunization
Interferon-gamma was the principal cytokine produced after primary measles
immunization, suggesting primary measles immunization induces predominantly a
TH1 type response.
4: Low natural killer cell cytotoxic activity in autism: the role of
glutathione, IL-2 and IL-15.
Vojdani A, Mumper E, Granpeesheh D, Mielke L, Traver D, Bock K, Hirani K,
Neubrander J, Woeller KN, O'Hara N, Usman A, Schneider C, Hebroni F, Berookhim
J, McCandless J.
J Neuroimmunol. 2008 Dec 15;205(1-2):148-54.
Although many articles have reported immune abnormalities in autism, NK cell
activity has only been examined in one study of 31 patients, of whom 12 were
found to have reduced NK activity. The mechanism behind this low NK cell
activity was not explored. For this reason, we explored the measurement of NK
cell activity in 1027 blood samples from autistic children obtained from ten
clinics and compared the results to 113 healthy controls. This counting of NK
cells and the measurement of their lytic activity enabled us to express the NK
cell activity/100 cells. At the cutoff of 15-50 LU we found that NK cell
activity was low in 41-81% of the patients from the different clinics. This NK
cell activity below 15 LU was found in only 8% of healthy subjects (p <0.001).
Low NK cell activity in both groups did not correlate with percentage and
absolute number of CD16(+)/CD56(+) cells. When the NK cytotoxic activity was
expressed based on activity/100 CD16(+)/CD56(+) cells, several patients who had
displayed NK cell activity below 15 LU exhibited normal NK cell activity.
Overall, after this correction factor, 45% of the children with autism still
exhibited low NK cell activity, correlating with the intracellular level of
glutathione. Finally, we cultured lymphocytes of patients with low or high NK
cell activity/cell with or without glutathione, IL-2 and IL-15. The induction of
NK cell activity by IL-2, IL-15 and glutathione was more pronounced in a
subgroup with very low NK cell activity. We conclude that that 45% of a subgroup
of children with autism suffers from low NK cell activity, and that low
intracellular levels of glutathione, IL-2 and IL-15 may be responsible.
5. Natural killer cell activity during measles.
Griffin DE et al.
Clin Exp Immunol. 1990 Aug;81(2):218-24.
Natural killer cells are postulated to play an important role in host anti-viral
defences. We measured natural killer cell activity in 30 individuals with acute
measles (73 +/- 21 lytic units (LU)/10(7) cells) and 16 individuals with other
infectious diseases (149 +/- 95 LU) and found it reduced compared with values
for adults (375 +/- 70 LU; P less than 0.001) or children (300 +/- 73 LU, P less
than 0.01) without infection. Reduced natural killer cell activity was found in
measles patients with (84 +/- 30 LU) and without (55 +/- 18 LU) complications
and was present for at least 3 weeks after the onset of the rash. Activity was
increased by in vitro exposure of cells to interleukin-2. Depressed natural
killer cell activity parallels in time the suppression of other parameters of
cell-mediated immunity that occurs during measles.