Re: Re: Lowly Cytokine May Play Role In Controlling Neurotransmitters

[Guest guest]

The abstract from the Journal of Clinical Allergy and Immunology

looks like it is from a presentation at a meeting. Some of the

professional societies publish the meeting abstracts in the journal.

Below is the abstract of a published paper on the same topic,

published later last year, by the same authors, in the Journal

of Immunology. This is where the full data are likely to be.

It's very exciting work. We definitely need 'before and after'

data, to determine how the various treatments for autism, results

in terms of autism, other symptoms (intestinal, etc.), and inflammatory

mediators are related (or not) to each other.

J Neuroimmunol 2001 Nov 1;120(1-2):170-9

Proinflammatory and regulatory cytokine production associated

with innate and adaptive immune responses in children with autism

spectrum disorders and developmental regression.

Jyonouchi H, Sun S, Le H.

Department of Pediatrics, University of Minnesota, MMC 610 FUMC,

420 Delaware Street SE, Minneapolis, MN 55455, USA. jyono001@...

We determined innate and adaptive immune responses in children

with developmental regression and autism spectrum disorders (ASD,

N=71), developmentally normal siblings (N=23), and controls (N=17).

With lipopolysaccharide (LPS), a stimulant for innate immunity,

peripheral blood

mononuclear cells (PBMCs) from 59/71 (83.1%) ASD patients produced

>2 SD above the control mean (CM) values of TNF-alpha, IL-1beta,

and/or IL-6 produced by control PBMCs. ASD PBMCs produced higher

levels of proinflammatory/counter-regulatory cytokines without

stimuli than controls. With

stimulants of phytohemagglutinin (PHA), tetanus, IL-12p70, and

IL-18, PBMCs from 47.9% to 60% of ASD patients produced >2 SD

above the CM values of TNF-alpha depending on stimulants. Our

results indicate excessive innate immune responses in a number

of ASD children that may be most evident in TNF-alpha production.

PMID: 11694332 [PubMed - indexed for MEDLINE]

G. Kahler, MD

>--- Original Message ---

>From: M Pappadia <pappadia@...>

>

>Date: 3/31/02 8:31:13 AM

>

>What studies are those?

>

>

>On Thu, 28 Mar 2002 23:14:00 -0800 " Cheryl B " <clbro66@...>

>writes:

>> Thanks, I couldn't remember what researcher had those findings.

The

>> cytokines being expressed will vary due to a number of factors.

>> There are

>> also many different cytokines, so testing usually looks at

the most

>> common

>> members of the family. The immune profiling studies

will

>> separate the

>> children into subgroups based on their cytokine profile rather

than

>> diagnosis.

>>

>> The abstract below is similar but includes a few other cytokines.

>> Cheryl

>>

>> The Journal of Allergy and Clinical Immunology

>>

>> February 2001, part 2 • Volume 107 • Number 2

>>

>> 897 Innate and Adaptive Immune Responses in Children With

>> Regression

>> Autism: Evaluation of the Effects of Environmental Factors

Including

>>

>> Vaccination

>>

>> Harumi Jyonouchi

>> Sining Sun

>> Hoa Le

>> University of Minnesota,

>> Minneapolis, MN

>>

>>

>> Etiology of autism is unknown. However, there appears to be

a casual

>>

>> association between onset of regression/autistic behavior

and infant

>>

>> immunization/viral infection/adverse reactions to common food

>> antigens

>> (gluten and cow’s milk). Previous literature indicates the

presence

>> of

>> autoantibodies against neuronal cells in autistic children

and

>> subtle immune

>> abnormalities such as skewed T2 responses. In this study,

we

>> hypothesized

>> that children with regression autism may have aberrant immune

>> responses

>> against these common, usually benign environmental factors,

>> resulting in

>> inflammatory and/or autoimmune conditions in the CNS. As a

first

>> step to

>> examine our hypothesis, we determined innate and adaptive

immune

>> responses

>> in children with autism spectrum disorders (N=35, Age 2-14

yrs,

>> median: 6

>> yr, 24 males and 9 females). Innate immune responses are assessed

by

>>

>> measuring production of TNF-, IL-1, IL-6, sTNFRI, and sTNFRII

after

>> incubating peripheral blood mononuclear (PBMN) cells overnight

with

>> endotoxin (LPS: 0.1 to 10 µg/ml). Adaptive immune responses

are

>> assessed by

>> measuring T cell cytokine (IFN-, IL-4, IL-5 and IL-10) production

in

>> response to recall antigens (tetanus and dust mite), mitogens

(PHA

>> and Con

>> A) and IFN- inducing cytokines (IL-12p70 and IL-18) after

culturing

>> cells

>> for 4 days with these stimuli. Production of IL-12p40, IL-18,

and

>> TGF- was

>> also measured in this setting. Controls were obtained from

healthy

>> normal

>> children (N=17, Age 2-16 yrs, median: 11 yrs). Onset of

>> autism/developmental

>> regression with immunization was reported in 27/35 patients

and

>> 32/35

>> patients were reported to have improvement of behavior by

>> parents/teachers/therapists with a casein-free/gluten-free

diet.

>> Autistic

>> children produced higher TNF- (p<0.01), stnfrii (p=0.038),

and il-6

> (p=0.01)

>> with a low dose of LPS (0.1 µg/ml) than controls. This is

due to the

>>

>> presence of a subset of patients who produced large amounts

of these

>>

>> cytokines. In fact, 27/35 (77.1%) study subjects produced

higher

>> than the

>> maximum levels of TNF-, sTNFRII, IL-6 and/or IL-1 observed

in

>> controls with

>> a low dose of LPS. We also observed elevated serum levels

of these

>> cytokines

>> in 8/18 autistic children. Our results thus indicate a high

>> frequency of

>> excessive innate immune responses in children with regression

>> autism. These

>> results may partly explain apparent association between onset

of

>> regression/autistic behavior and immunization in these children.

>> Production

>> of IFN-, IL-5, IL-10 and IL-12p40 was highly variable in autistic

>> children.

>> IL-4, IL-18, and TGF- production by PBMN cells were generally

low

>> and did

>> not differ between the study subjects and controls. We also

assessed

>> T1/T2

>> responses by comparing the ratio of IFN-/IL-5 levels produced

with

>> recall

>> antigens. The ratio of IFN-/IL-5 did not differ between autistic

>> children

>> and controls. However, 7 and 8 out of 35 autistic children

produced

>> significantly high IL-12p40 with recall antigens and IL-12/IL-18,

>> respectively. IL-10 production was markedly variable in autistic

>> children:

>> 10 and 11 out of 35 subjects produced high amounts of IL-10

with PHA

>> and

>> tetanus, respectively, while 12/35 subjects produced significantly

>> low IL-10

>> with PHA as compared to controls. These results also indicate

>> aberrant

>> production of regulatory cytokines for T cell responses in

subsets

>> of

>> autistic children.

>>

>-------------------------------------------------------------------------

>-------

>>

>> >From: " Jon " <jerseybean@...>

>> >Reply-

>> ><nids >

>> >Subject: Re: Lowly Cytokine May Play Role In Controlling

>> >Neurotransmitters

>> >Date: Thu, 28 Mar 2002 20:07:49 -0000

>> >

>> >Cheryl,

>> >

>> >It was Dr Jyonouchi, you are right about TNF-a being elevated

for

>> some.

>> >

>> >Jon.

>> >

>>

>>------------------------------------------------------------------------

>--------

>> > 1: J Neuroimmunol 2001 Nov 1;120(1-2):170-9

>> >

>> >

>> >Proinflammatory and regulatory cytokine production associated

with

>> innate

>> >and adaptive immune responses in children with autism spectrum

>> disorders

>> >and developmental regression.

>> >

>>

>>

>> _________________________________________________________________

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>>

>>

[Guest guest]

, thanks for the abstract. people like science.

Re: Lowly Cytokine May Play Role In Controlling

>

> >> >Neurotransmitters

> >> >Date: Thu, 28 Mar 2002 20:07:49 -0000

> >> >

> >> >Cheryl,

> >> >

> >> >It was Dr Jyonouchi, you are right about TNF-a being elevated

> for

> >> some.

> >> >

> >> >Jon.

> >> >

> >>

> >>------------------------------------------------------------------------

> >--------

> >> > 1: J Neuroimmunol 2001 Nov 1;120(1-2):170-9

> >> >

> >> >

> >> >Proinflammatory and regulatory cytokine production associated

> with

> >> innate

> >> >and adaptive immune responses in children with autism spectrum

>

> >> disorders

> >> >and developmental regression.

> >> >

> >>

> >>

> >> _________________________________________________________________

> >> MSN Photos is the easiest way to share and print your photos:

>

> >> http://photos.msn.com/support/worldwide.aspx

> >>

> >>

> >>

> >>