interleukin-6

[Guest guest]

Pardon my ingorance but what is interleukin 6?

Message: 6

Date: Sun, 09 Apr 2006 00:33:48 -0400

From: Doris and Steve <sjsmith@...>

Subject: prenatal exposure to IL6

Subject: Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

m J Physiol Regul Integr Comp Physiol 290: R1345-R1356, 2006

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in

hippocampus with NMDA/GABAA dysregulation and impaired spatial learning

Anne-Maj sson,1 Eva Jennische,2 Hans-Arne Hansson,2 and Agneta Holmäng1

1Cardiovascular Institute and Wallenberg Laboratory and 2Institute of Anatomy

and Cell Biology, Göteborg University, Sahlgrenska Academy, Göteborg, Sweden

During pregnancy, infection or immune responses induce cytokine release, which

might influence fetal neurodevelopment, leading to neurodegenerative disease in

adulthood. Because the hippocampus is a key area for learning and memory, we

evaluated 4- and 24-wk-old rats for the effects of early and late prenatal

exposure to interleukin-6 (IL-6) on hippocampal morphology, expression of mRNA

for IL-6, the -aminobutyric acid receptor (GABAA5), the NR1 subunit of the

N-methyl-D-aspartate receptor, and glial fibrillary acidic protein (GFAP),

caspase-3 protein and mRNA levels, and learning abilities. Late exposure

increased serum IL-6 and hippocampal expression of IL-6 mRNA at 4 and 24 wk. All

adult rats showed neuronal loss in the hilus and astrogliosis; males had losses

mainly in the CA2 and CA3 regions, and females in CA1. Expression of GABAA5,

NR1, and GFAP mRNA increased in late-exposed males and females at 4 and 24 wk.

mRNA and protein levels of the apoptosis marker caspase-3 were increased in all

late-exposed rats except males at 4 wk. Evaluation of hippocampus-dependent

working memory in the water maze at 20 wk of age showed increases in

escape latency and time spent near the pool wall in all IL-6 adult rats,

especially females. These findings suggest that fetal IL-6 exposure, especially

in late pregnancy, leads to increased IL-6 levels in the circulation and

hippocampus, abnormalities of hippocampal structural and morphology, and

decreased learning during adulthood.

intrauterine exposure; hippocampus; cytokine; spatial learning; water maze

[Guest guest]

no ignorance because we're all still toodling around

the immune pool

I know that IL-6 is a part of the immune system.

SOMEWHERE I have a website that explains what the

ILs are ... and what they do ...

I interpreted this article as possible maternal

antibodies connection ...

prenatal and IL 6 exposure ...

Kathy? ? Cheryl? woohoo

suggestions?

doris

>

> Pardon my ingorance but what is interleukin 6?

>

> Message: 6

> Date: Sun, 09 Apr 2006 00:33:48 -0400

> From: Doris and Steve <sjsmith@...>

> Subject: prenatal exposure to IL6

>

> Subject: Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

>

> m J Physiol Regul Integr Comp Physiol 290: R1345-R1356, 2006

> DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

>

> Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration in hippocampus with NMDA/GABAA dysregulation and

impaired spatial learning

> Anne-Maj sson,1 Eva Jennische,2 Hans-Arne Hansson,2 and Agneta

Holmäng1

> 1Cardiovascular Institute and Wallenberg Laboratory and 2Institute

of Anatomy and Cell Biology, Göteborg University, Sahlgrenska Academy,

Göteborg, Sweden

>

>

> During pregnancy, infection or immune responses induce cytokine

release, which might influence fetal neurodevelopment, leading to

neurodegenerative disease in adulthood. Because the hippocampus is a

key area for learning and memory, we evaluated 4- and 24-wk-old rats

for the effects of early and late prenatal exposure to interleukin-6

(IL-6) on hippocampal morphology, expression of mRNA for IL-6, the

-aminobutyric acid receptor (GABAA5), the NR1 subunit of the

N-methyl-D-aspartate receptor, and glial fibrillary acidic protein

(GFAP), caspase-3 protein and mRNA levels, and learning abilities.

Late exposure increased serum IL-6 and hippocampal expression of IL-6

mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the hilus

and astrogliosis; males had losses mainly in the CA2 and CA3 regions,

and females in CA1. Expression of GABAA5, NR1, and GFAP mRNA increased

in late-exposed males and females at 4 and 24 wk. mRNA and protein

levels of the apoptosis marker caspase-3 were increased in all

late-exposed rats except males at 4 wk. Evaluation of

hippocampus-dependent working memory in the water maze at 20 wk

of age showed increases in escape latency and time spent near the pool

wall in all IL-6 adult rats, especially females. These findings

suggest that fetal IL-6 exposure, especially in late pregnancy, leads

to increased IL-6 levels in the circulation and hippocampus,

abnormalities of hippocampal structural and morphology, and decreased

learning during adulthood.

>

> intrauterine exposure; hippocampus; cytokine; spatial learning;

water maze

>

[Guest guest]

It’s a cytokine or messenger protein in the immune system that tells the

system what to---ie release NK cells, or T cells etc - if you go to the

website that Doris posted yesterday you will see a list of all of them...

http://en.wikipedia.org/wiki/Interleukins

These are believed to be integral in the dysfunction of our kids -

especially IL 10 and 12. Some of the viruses like EBV, or CMV or HHV 6 (or

retroviruses that are mutations of theses) produce proteins that mimic the

interleukins that send off the wrong message to the white cells and cause

the improper immune response ...(please - a very simplistic explanation

that may not be totally accurate but I think gives the general idea of what

is happening)

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

m J Physiol Regul Integr Comp Physiol 290: R1345-R1356, 2006

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration

in hippocampus with NMDA/GABAA dysregulation and impaired spatial learning

Anne-Maj sson,1 Eva Jennische,2 Hans-Arne Hansson,2 and Agneta

Holmäng1

1Cardiovascular Institute and Wallenberg Laboratory and 2Institute of

Anatomy and Cell Biology, Göteborg University, Sahlgrenska Academy,

Göteborg, Sweden

During pregnancy, infection or immune responses induce cytokine release,

which might influence fetal neurodevelopment, leading to neurodegenerative

disease in adulthood. Because the hippocampus is a key area for learning and

memory, we evaluated 4- and 24-wk-old rats for the effects of early and late

prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology,

expression of mRNA for IL-6, the -aminobutyric acid receptor (GABAA5), the

NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary

acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning

abilities. Late exposure increased serum IL-6 and hippocampal expression of

IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the hilus

and astrogliosis; males had losses mainly in the CA2 and CA3 regions, and

females in CA1. Expression of GABAA5, NR1, and GFAP mRNA increased in

late-exposed males and females at 4 and 24 wk. mRNA and protein levels of

the apoptosis marker caspase-3 were increased in all late-exposed rats

except males at 4 wk. Evaluation of hippocampus-dependent working memory in

the water maze at 20 wk of age showed increases in escape latency and

time spent near the pool wall in all IL-6 adult rats, especially females.

These findings suggest that fetal IL-6 exposure, especially in late

pregnancy, leads to increased IL-6 levels in the circulation and

hippocampus, abnormalities of hippocampal structural and morphology, and

decreased learning during adulthood.

intrauterine exposure; hippocampus; cytokine; spatial learning; water maze

Responsibility for the content of this message lies strictly with

the original author(s), and is not necessarily endorsed by or the

opinion of the Research Institute and/or the Parent Coalition.

[Guest guest]

These posts on IL-6 caught my eye, as when my son was first having

issues at 2.5 we did some extensive testing through a “DAN” doctor, but

then elected not to pursue the protocol. In any event, some of the

testing that we did was a “genetic” profile of various SNP mutations

thought to maybe affect ASD kids which included all sorts of areas, the

profile showed whether there were mutations in genes and whether my son

had a normal SNP or whether there was a mutation from one or both of his

parents. Anyway, IL-6 was listed under vascular integrity section and

my son showed a mutation from both of us. I have always wondered what

this meant. Of course, the DAN doc who ordered it couldn’t explain the

significance and I quite frankly just forgot about it. Now that I am

aware of the theory and all of the current research out there on

the immune system and inflammation, I am curious whether anyone knows

anything about possible genetic predispositions to problems with the

immune system. I am curious as to whether his particular mutation

existed prior to whatever environmental insult (virus, bacteria, etc)

affected his immune system and caused the downward spiral or whether the

insult caused the particular genetic SNP to “overexpress” (for lack of a

better word). Does this make sense? ? Does it even matter as far as

treatment goes, I presume not? Sorry for the ramble, this is just very

interesting.

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

m J Physiol Regul Integr Comp Physiol 290: R1345-R1356, 2006

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

in hippocampus with NMDA/GABAA dysregulation and impaired spatial

learning

Anne-Maj sson,1 Eva Jennische,2 Hans-Arne Hansson,2 and Agneta

Holmäng1

1Cardiovascular Institute and Wallenberg Laboratory and 2Institute of

Anatomy and Cell Biology, Göteborg University, Sahlgrenska Academy,

Göteborg, Sweden

During pregnancy, infection or immune responses induce cytokine release,

which might influence fetal neurodevelopment, leading to

neurodegenerative

disease in adulthood. Because the hippocampus is a key area for learning

and

memory, we evaluated 4- and 24-wk-old rats for the effects of early and

late

prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology,

expression of mRNA for IL-6, the -aminobutyric acid receptor (GABAA5),

the

NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary

acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning

abilities. Late exposure increased serum IL-6 and hippocampal expression

of

IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the

hilus

and astrogliosis; males had losses mainly in the CA2 and CA3 regions,

and

females in CA1. Expression of GABAA5, NR1, and GFAP mRNA increased in

late-exposed males and females at 4 and 24 wk. mRNA and protein levels

of

the apoptosis marker caspase-3 were increased in all late-exposed rats

except males at 4 wk. Evaluation of hippocampus-dependent working memory

in

the water maze at 20 wk of age showed increases in escape latency

and

time spent near the pool wall in all IL-6 adult rats, especially

females.

These findings suggest that fetal IL-6 exposure, especially in late

pregnancy, leads to increased IL-6 levels in the circulation and

hippocampus, abnormalities of hippocampal structural and morphology, and

decreased learning during adulthood.

intrauterine exposure; hippocampus; cytokine; spatial learning; water

maze

Responsibility for the content of this message lies strictly with

the original author(s), and is not necessarily endorsed by or the

opinion of the Research Institute and/or the Parent Coalition.

[Guest guest]

this is very interesting... you might raise this with Dr Goldberg.. he

has always said (and I note others are increasingly saying this - like

Wakefiled, Shattock, Bradstreet - just this week) that our kids are likely

to have a genetic predisposition to an immune dysfunction... and it might be

more than one. This genetic predisposition may be present in many more

people - and in ASD kids particularly family - siblings, parents,

grandparents and may manifest itself in different ways at different ages (or

not at all) depending on certain triggers. Interesting that you had some

genetic profiling done that threw out the IL-6 reference. We have seen

reference over recent years to abnormalities in this gene or that gene in

ASD kids. However unless the researchers look for immune dysfunctional genes

in ASD kids first and profile these, it seems few consistent answers will be

found and not much headway will be made in the genetic link.

Are you able to go back to these results and investigate them further?

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

m J Physiol Regul Integr Comp Physiol 290: R1345-R1356, 2006

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

in hippocampus with NMDA/GABAA dysregulation and impaired spatial

learning

Anne-Maj sson,1 Eva Jennische,2 Hans-Arne Hansson,2 and Agneta

Holmäng1

1Cardiovascular Institute and Wallenberg Laboratory and 2Institute of

Anatomy and Cell Biology, Göteborg University, Sahlgrenska Academy,

Göteborg, Sweden

During pregnancy, infection or immune responses induce cytokine release,

which might influence fetal neurodevelopment, leading to

neurodegenerative

disease in adulthood. Because the hippocampus is a key area for learning

and

memory, we evaluated 4- and 24-wk-old rats for the effects of early and

late

prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology,

expression of mRNA for IL-6, the -aminobutyric acid receptor (GABAA5),

the

NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary

acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning

abilities. Late exposure increased serum IL-6 and hippocampal expression

of

IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the

hilus

and astrogliosis; males had losses mainly in the CA2 and CA3 regions,

and

females in CA1. Expression of GABAA5, NR1, and GFAP mRNA increased in

late-exposed males and females at 4 and 24 wk. mRNA and protein levels

of

the apoptosis marker caspase-3 were increased in all late-exposed rats

except males at 4 wk. Evaluation of hippocampus-dependent working memory

in

the water maze at 20 wk of age showed increases in escape latency

and

time spent near the pool wall in all IL-6 adult rats, especially

females.

These findings suggest that fetal IL-6 exposure, especially in late

pregnancy, leads to increased IL-6 levels in the circulation and

hippocampus, abnormalities of hippocampal structural and morphology, and

decreased learning during adulthood.

intrauterine exposure; hippocampus; cytokine; spatial learning; water

maze

Responsibility for the content of this message lies strictly with

the original author(s), and is not necessarily endorsed by or the

opinion of the Research Institute and/or the Parent Coalition.

[Guest guest]

,

You do make sense... unfortunately, I don't know enough to give you an

answer though. One question did ask Dr. Goldberg once was whether or not a

" defective " gene could have a role in our boys' condition. We have 5

kids and the two that have look very much alike and share many

features... they look more alike than any of the others... it's the sort of

thing where we look a baby picture and could get them mixed up if we didn't

know the time frame of the photo.

Anyway, we asked if theoretically the two boys could have a defective gene

that would prevent their immune systems from ever functioning normally and

he sort of downplayed that idea... I can't remember exactly what he said,

though. He didn't seem very caught up in our theory.

Our boys have shown improvement on the protocol... the younger one responded

more quickly than the older (the younger was also put on meds at age 3

instead of almost 7 in the older son's case... oh, that I hade those years

back to do things differently).

That's all I know... Not much help. Sorry!

Caroline

> From: " K. Fischer " <elfischer@...>

> Reply-< >

> Date: Fri, 21 Apr 2006 08:40:11 -0500

> < >

> Subject: RE: interleukin-6

>

> These posts on IL-6 caught my eye, as when my son was first having

> issues at 2.5 we did some extensive testing through a ³DAN² doctor, but

> then elected not to pursue the protocol. In any event, some of the

> testing that we did was a ³genetic² profile of various SNP mutations

> thought to maybe affect ASD kids which included all sorts of areas, the

> profile showed whether there were mutations in genes and whether my son

> had a normal SNP or whether there was a mutation from one or both of his

> parents. Anyway, IL-6 was listed under vascular integrity section and

> my son showed a mutation from both of us. I have always wondered what

> this meant. Of course, the DAN doc who ordered it couldn¹t explain the

> significance and I quite frankly just forgot about it. Now that I am

> aware of the theory and all of the current research out there on

> the immune system and inflammation, I am curious whether anyone knows

> anything about possible genetic predispositions to problems with the

> immune system. I am curious as to whether his particular mutation

> existed prior to whatever environmental insult (virus, bacteria, etc)

> affected his immune system and caused the downward spiral or whether the

> insult caused the particular genetic SNP to ³overexpress² (for lack of a

> better word). Does this make sense? ? Does it even matter as far as

> treatment goes, I presume not? Sorry for the ramble, this is just very

> interesting.

>

>

[Guest guest]

,

My son no longer sees the DAN doctor that did the testing and couldn’t

explain it, BUT I have thought about taking the results (which I have

full copies of) to a geneticist to see if they could investigate it

further. I guess I would need to find one that had an interest and

knowledge in immunology and genetics. Interestingly, on my father’s

side: my grandfather had meningitis as a teenager and his daughter (my

aunt) had viral encephalitis as a child, nearly died. My father has a

weak immune system, as do I. My son’s condition occurred during

various serious ear infections and an illness, looking back I think

there was definitely an acute inflammatory infection, I just didn’t

recognize it. Anyway, I have always thought it a strange coincidence

that these close relatives could have serious infections of the central

nervous system at such an early age. Anyway, , you noted that

others were talking about this genetic component, was it at a

conference? Just curious.

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

m J Physiol Regul Integr Comp Physiol 290: R1345-R1356, 2006

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

in hippocampus with NMDA/GABAA dysregulation and impaired spatial

learning

Anne-Maj sson,1 Eva Jennische,2 Hans-Arne Hansson,2 and Agneta

Holmäng1

1Cardiovascular Institute and Wallenberg Laboratory and 2Institute of

Anatomy and Cell Biology, Göteborg University, Sahlgrenska Academy,

Göteborg, Sweden

During pregnancy, infection or immune responses induce cytokine release,

which might influence fetal neurodevelopment, leading to

neurodegenerative

disease in adulthood. Because the hippocampus is a key area for learning

and

memory, we evaluated 4- and 24-wk-old rats for the effects of early and

late

prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology,

expression of mRNA for IL-6, the -aminobutyric acid receptor (GABAA5),

the

NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary

acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning

abilities. Late exposure increased serum IL-6 and hippocampal expression

of

IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the

hilus

and astrogliosis; males had losses mainly in the CA2 and CA3 regions,

and

females in CA1. Expression of GABAA5, NR1, and GFAP mRNA increased in

late-exposed males and females at 4 and 24 wk. mRNA and protein levels

of

the apoptosis marker caspase-3 were increased in all late-exposed rats

except males at 4 wk. Evaluation of hippocampus-dependent working memory

in

the water maze at 20 wk of age showed increases in escape latency

and

time spent near the pool wall in all IL-6 adult rats, especially

females.

These findings suggest that fetal IL-6 exposure, especially in late

pregnancy, leads to increased IL-6 levels in the circulation and

hippocampus, abnormalities of hippocampal structural and morphology, and

decreased learning during adulthood.

intrauterine exposure; hippocampus; cytokine; spatial learning; water

maze

Responsibility for the content of this message lies strictly with

the original author(s), and is not necessarily endorsed by or the

opinion of the Research Institute and/or the Parent Coalition.

[Guest guest]

Others have made comments about Genetic I read very recently - I think in a

Schafer report

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

m J Physiol Regul Integr Comp Physiol 290: R1345-R1356, 2006

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

in hippocampus with NMDA/GABAA dysregulation and impaired spatial

learning

Anne-Maj sson,1 Eva Jennische,2 Hans-Arne Hansson,2 and Agneta

Holmäng1

1Cardiovascular Institute and Wallenberg Laboratory and 2Institute of

Anatomy and Cell Biology, Göteborg University, Sahlgrenska Academy,

Göteborg, Sweden

During pregnancy, infection or immune responses induce cytokine release,

which might influence fetal neurodevelopment, leading to

neurodegenerative

disease in adulthood. Because the hippocampus is a key area for learning

and

memory, we evaluated 4- and 24-wk-old rats for the effects of early and

late

prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology,

expression of mRNA for IL-6, the -aminobutyric acid receptor (GABAA5),

the

NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary

acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning

abilities. Late exposure increased serum IL-6 and hippocampal expression

of

IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the

hilus

and astrogliosis; males had losses mainly in the CA2 and CA3 regions,

and

females in CA1. Expression of GABAA5, NR1, and GFAP mRNA increased in

late-exposed males and females at 4 and 24 wk. mRNA and protein levels

of

the apoptosis marker caspase-3 were increased in all late-exposed rats

except males at 4 wk. Evaluation of hippocampus-dependent working memory

in

the water maze at 20 wk of age showed increases in escape latency

and

time spent near the pool wall in all IL-6 adult rats, especially

females.

These findings suggest that fetal IL-6 exposure, especially in late

pregnancy, leads to increased IL-6 levels in the circulation and

hippocampus, abnormalities of hippocampal structural and morphology, and

decreased learning during adulthood.

intrauterine exposure; hippocampus; cytokine; spatial learning; water

maze

Responsibility for the content of this message lies strictly with

the original author(s), and is not necessarily endorsed by or the

opinion of the Research Institute and/or the Parent Coalition.