Alcohol reducing symptoms of autism in some individuals

[Guest guest]

forwarding this from another list - are there any people on this list with adult ASD kids? I was wondering if any tended to drank wine (or other alcohol), and if noticed any changes in 'autism'?....I was very intrigued by something posted on another

board. In this link a woman is saying her child (adult Aspie) seems more typical after

drinking alcohol and that he doesn't seem drunk at all. If this was

across the board with all ASD kids/adults or even very common it might

point to something in that is worth looking into.

Indeed one comment left on board confirmed the effects in another ASD

individual. http://youtube.com/watch?v=MWXLiTcq4y0

I have had a quick look through literature and it turns up alcohol, esp.

some types of drinks, decrease inflammatory responses. Sometimes

dramatically. It is well know that chronic long-term

consumption/intoxification messes up the immune system…

I have copied some most interesting abstracts here, wonder if anyone

would have any thoughts on this, or maybe some other mechanisms that

could be at work…

Natasa

Atherosclerosis. 2007 Jun;192(2):335-41. Epub 2006 Sep 12.

Ethanol beverages containing polyphenols decrease nuclear factor kappa-B

activation in mononuclear cells and circulating MCP-1 concentrations in

healthy volunteers during a fat-enriched diet.

Blanco-Colio LM..

AIMS: Different epidemiological studies have demonstrated that some

ethanol containing beverages intake could be associated with a reduction

of cardiovascular mortality, effect attributed in part to its

antioxidant properties. Nuclear factor-kappa B (NF-kappaB) is a redox

sensitive transcription factor implicated in the pathogenesis of

atherosclerosis. We have examined the effect of four different ethanol

containing beverages on the activation of NF-kappaB in peripheral blood

mononuclear cells (PBMC) and circulating concentrations of monocyte

chemoattractant protein-1 (MCP-1) in healthy volunteers receiving a

fat-enriched diet. METHODS AND RESULTS: Sixteen volunteers received 16

g/m(2) of ethanol in form of red wine, spirits (vodka, rum, and brandy)

or no ethanol intake along with a fat-enriched diet during 5 days and

all of them took all alcohols at different periods. NF-kappaB activation

(electrophoretic mobility shift assay) and circulating MCP-1 levels

(ELISA) were examined in blood samples taken before and after 5 days of

ethanol intake. Subjects receiving a fat-enriched diet had increased

NF-kappaB activation in PBMC at day 5. Furthermore, MCP-1 levels were

increased in plasma at day 5. Red wine intake and some ethanol beverages

containing polyphenols (brandy and rum) prevented NF-kappaB activation

and decreased MCP-1 release. CONCLUSION: Consumption of moderate amounts

of alcoholic drinks containing polyphenols decreases NF-kappaB

activation in PBMCs and MCP-1 plasma levels during a fat-enriched diet.

Our results provide additional evidence of the anti-inflammatory effects

of some ethanol containing beverages, further supporting the idea that

its moderate consumption may help to reduce overall cardiovascular

mortality.

Publication Types: * Research Support, Non-U.S. Gov't

PMID: 16970955 [PubMed - indexed for MEDLINE]

2: Alcohol Clin Exp Res. 2005 Jul;29(7):1198-205.

Effects of systemic and local CXC chemokine administration on the

ethanol-induced suppression of pulmonary neutrophil recruitment.

Quinton LJ, S, Zhang P, Happel KI, Gamble L, Bagby GJ.

Department of Physiology, Louisiana State University Health Sciences

Center, New Orleans, Louisiana 70112, USA.

BACKGROUND: Acute alcohol intoxication impairs the neutrophil

response to intrapulmonary infection, resulting in impaired host defense

and increased patient morbidity and mortality. We recently showed that

intratracheal (IT) chemokine administration promotes pulmonary

neutrophil migration in rats and that this process is enhanced by

systemic administration of the Glu-Leu-Arg (ELR+) and CXC chemokine

cytokine-induced neutrophil chemoattractant (CINC). Here we hypothesized

that exogenous chemokine administration would mitigate the suppressive

effect of alcohol on neutrophil recruitment into the lung. METHODS:

Macrophage inflammatory protein-2 (MIP-2), a rat ELR+ CXC chemokine, or

live Klebsiella pneumoniae (K. pneumoniae) was administered it to induce

alveolar neutrophil migration in the absence or presence of acute

ethanol intoxication. Depending on the experimental protocol, rats

received either intravenous (IV) CINC or IT chemokines (CINC and MIP-2)

20 min after it MIP-2 or K. pneumoniae. Rats were euthanized 90 min or

four hr after the first IT injection for sample collection. RESULTS:

Neutrophil counts were significantly elevated in bronchoalveolar lavage

fluid (BALF) of rats receiving IT MIP-2 compared with vehicle-treated

rats, and this response was significantly decreased in animals

pretreated with ethanol. CINC IV enhanced the neutrophil response to IT

MIP-2 in both the absence and presence of acute ethanol intoxication. In

rats challenged with K. pneumoniae, ethanol pretreatment significantly

reduced BALF levels of CINC and MIP-2, suppressed alveolar neutrophil

recruitment, and decreased whole-lung myeloperoxidase activity. CINC IV

did not alter BALF neutrophil counts in the absence or presence of

ethanol administration 4 hr after IT K. pneumoniae. Alternatively, IT

chemokine instillation partially restored BALF neutrophil recruitment

but not whole-lung myeloperoxidase activity in ethanol-treated rats.

CONCLUSIONS: Ethanol significantly inhibits the pulmonary inflammatory

responses to both MIP-2 and K. pneumoniae. Exogenous chemokine

administration may be a useful means to enhance host defenses in the

ethanol-intoxicated host, although the results of this study also

indicate that ethanol intoxication can impair neutrophil recruitment,

independent of its effects on local chemotactic gradients.

Publication Types: PMID: 16046875 [PubMed - indexed for MEDLINE]

3: Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1669-75. Epub 2005

May 20.

Ethanol inhibits monocyte chemotactic protein-1 expression in

interleukin-1{beta}-activated human endothelial cells.

Cullen JP, Sayeed S, Jin Y, Theodorakis NG, Sitzmann JV, Cahill PA,

Redmond EM. Department of Surgery, University of Rochester Medical

Center, Rochester, New York 14642, USA.

The aim of this study was to determine the effect of ethanol (EtOH)

on endothelial monocyte chemotactic protein-1 (MCP-1) expression.

IL-1beta increased the production of MCP-1 by human umbilical vein

endothelial cells from undetectable levels to approximately 900 pg/ml at

24 h. EtOH dose-dependently inhibited IL-1beta-stimulated MCP-1

secretion as determined by ELISA: 25 +/- 1%, 35 +/- 7%, and 65 +/- 5%

inhibition for 1, 10, and 100 mM EtOH, respectively, concomitant with

inhibition of monocyte adhesion to activated endothelial cells.

Similarly, EtOH dose-dependently inhibited IL-1beta-stimulated MCP-1

mRNA expression. Experiments with actinomycin D demonstrated that EtOH

decreased the stability of MCP-1 mRNA. In addition, EtOH significantly

reduced NF-kappaB and AP-1 binding activity induced by IL-1beta and

inhibited MCP-1 gene transcription. Binding of (125)I-labeled MCP-1 to

its receptor (CCR2) on THP-1 human monocytic cells was not affected by

EtOH treatment. Modulation of the expression of MCP-1 represents a

mechanism whereby EtOH could inhibit atherogenesis by blocking the

crucial early step of monocyte adhesion and subsequent recruitment to

the subendothelial space. These actions of EtOH may underlie, in part,

its cardiovascular protective effects in vivo.

Publication Types:

PMID: 15908470 [PubMed - indexed for MEDLINE]

4: J Immunol. 2004 Nov 15;173(10):6376-83.

Ethanol blocks leukocyte recruitment and endothelial cell activation in

vivo and in vitro.

Saeed RW, Varma S, Peng T, Tracey KJ, Sherry B, Metz CN.

Laboratories of Medical Biochemistry, North Shore-Long Island Jewish

Research Institute, 350 Community Drive, Manhasset, NY 11030, USA.

Immune system impairment and increased susceptibility to infection

among alcohol abusers is a significant but not well-understood problem.

We hypothesized that acute ethanol administration would inhibit

leukocyte recruitment and endothelial cell activation during

inflammation and infection. Using LPS and carrageenan air pouch models

in mice, we found that physiological concentrations of ethanol (1-5

g/kg) significantly blocked leukocyte recruitment (50-90%). Because

endothelial cell activation and immune cell-endothelial cell

interactions are critical regulators of leukocyte recruitment, we

analyzed the effect of acute ethanol exposure on endothelial cell

activation in vivo using the localized Shwartzman reaction model. In

this model, ethanol markedly suppressed leukocyte accumulation and

endothelial cell adhesion molecule expression in a dose-dependent

manner. Finally, we examined the direct effects of ethanol on

endothelial cell activation and leukocyte-endothelial cell interactions

in vitro. Ethanol, at concentrations within the range found in human

blood after acute exposure and below the levels that induce cytotoxicity

(0.1-0.5%), did not induce endothelial cell activation, but

significantly inhibited TNF-mediated endothelial cell activation, as

measured by adhesion molecule (E-selectin, ICAM-1, VCAM-1) expression

and chemokine (IL-8, MCP-1, RANTES) production and leukocyte adhesion in

vitro. Studies exploring the potential mechanism by which ethanol

suppresses endothelial cell activation revealed that ethanol blocked

NF-kappaB nuclear entry in an IkappaBalpha-dependent manner. These

findings support the hypothesis that acute ethanol overexposure may

increase the risk of infection and inhibit the host inflammatory

response, in part, by blocking endothelial cell activation and

subsequent immune cell-endothelial cell interactions required for

efficient immune cell recruitment.

Publication Types: * Research Support, Non-U.S. Gov't

* Research Support, U.S. Gov't, P.H.S.

PMID: 15528377 [PubMed - indexed for MEDLINE]

5: J Immunol. 2004 Aug 15;173(4):2715-24.

Suppression of innate immunity by acute ethanol administration: a global

perspective and a new mechanism beginning with inhibition of signaling

through TLR3.

Pruett SB, Schwab C, Zheng Q, Fan R. Department of Cellular

Biology and Anatomy, Louisiana State University Health Sciences Center,

Shreveport, LA 71130, USA. spruet@...

Excessive consumption of ethanol (EtOH) suppresses innate immunity,

but the mechanisms have not been fully delineated. The present study was

conducted to determine whether EtOH suppresses TLR signaling in vivo in

mice and to characterize the downstream effects of such suppression.

Degradation of IL-1R-associated kinase 1 induced by a TLR3 ligand in

peritoneal cells ( approximately 90% macrophages) was suppressed by

EtOH. Phosphorylation of p38 kinase in peritoneal macrophages (F4/80(+))

was suppressed, as was nuclear translocation of p-c-Jun and p65 in

peritoneal cells. EtOH decreased IL-6 and IL-12 (p40), but did not

significantly affect IL-10 in peritoneal lavage fluid or in lysates of

peritoneal cells. Changes in cytokine mRNAs (by RNase protection assay)

in macrophages isolated by cell sorting or using Ficoll were generally

consistent with changes in protein levels in cell lysates and peritoneal

lavage fluid. Thus, suppression of TLR signaling and cytokine mRNA

occurred in the same cells, and this suppression generally corresponded

to changes in i.p. and intracellular cytokine concentrations. DNA

microarray analysis revealed the suppression of an IFN-related

amplification loop in peritoneal macrophages, associated with decreased

expression of numerous innate immune effector genes (including cytokines

and a chemokine also suppressed at the protein level). These results

indicate that EtOH suppresses innate immunity at least in part by

suppressing TLR3 signaling, suppressing an IFN-related amplification

loop, and suppressing the induction of a wide range of innate effector

molecules in addition to proinflammatory cytokines and chemokines.

Publication Types: * Research Support, U.S. Gov't, P.H.S.

PMID: 15294990 [PubMed - indexed for MEDLINE]

6: Atherosclerosis. 2004 Jul;175(1):117-23.

Different effects of red wine and gin consumption on inflammatory

biomarkers of atherosclerosis: a prospective randomized crossover trial.

Effects of wine on inflammatory markers.

Estruch R, Sacanella E, Badia E, Antúnez E, Nicolás JM,

Fernández-Solá J, Rotilio D, de Gaetano G, Rubin E,

Urbano-Márquez A. Department of Internal Medicine, Hospital

Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer

(IDIBAPS), University of Barcelona, Barcelona, Spain.

BACKGROUND: No intervention studies have explored the

anti-inflammatory effects of different alcoholic beverages on markers of

atherosclerosis. We embarked on a randomized, crossover, single-blinded

trial to evaluate the effects of wine and gin on inflammatory biomarkers

of atherosclerosis. METHODS AND RESULTS: Forty healthy men (mean age,

37.6 years) consumed 30 g ethanol per day as either wine or gin for 28

days. Before and after each intervention, we measured the expression of

lymphocyte function-associated antigen 1 (LFA-1), Mac-1, very late

activation antigen 4 (VLA-4), and monocyte chemoattractant protein

(MCP-1) in monocytes, as well as the soluble vascular cell adhesion

molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1),

interleukin-1alpha (IL-1alpha), C-reactive protein (hs-CRP) and

fibrinogen. After either gin or wine consumption, plasma fibrinogen

decreased by 5 and 9%, respectively, and cytokine IL-1alpha by 23 and

21%. The expression of LFA-1 (-27%), Mac-1 (-27%), VLA-4 (-32%) and

MCP-1 (-46%) decreased significantly after wine, but not after gin. Wine

reduced the serum concentrations of hs-CRP (-21%), VCAM-1 (-17%) and

ICAM-1 (-9%). CONCLUSIONS: Both wine and gin showed anti-inflammatory

effects by reducing plasma fibrinogen and IL-1alpha levels. However,

wine had the additional effect of decreasing hs-CRP, as well as monocyte

and endothelial adhesion molecules.

Publication Types:

PMID: 15186955 [PubMed - indexed for MEDLINE]

7: Scand J Gastroenterol. 2004 Mar;39(3):277-82.

Alcohol modulates circulating levels of interleukin-6 and monocyte

chemoattractant protein-1 in chronic pancreatitis.

Pedersen N, Larsen S, Seidelin JB, Nielsen OH Dept. of Medicine

M, Division of Gastroenterology, Glostrup Hospital, University of

Copenhagen, Denmark.

BACKGROUND: Cytokines are markers of acute pancreatic inflammation

and essential for distant organ injury, but they also stimulate

pancreatic fibrogenesis and are thus involved in the progression from

acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of

this study was to evaluate the circulating levels of IL-6, MCP-1,

TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic

pancreatitis (CP). METHODS: Twelve male patients with severe CP and 11

matched controls ingested 40 g alcohol. Plasma cytokine concentrations

were measured for 24 h and assessed by sandwich ELISA techniques.

RESULTS: IL-6 was higher in CP at fasting and 1, 4 and 24 h after

alcohol intake (P < 0.04), and a significantly greater rise was found at

1 h compared to pre-stimulatory conditions and controls (P < 0.01).

MCP-1 plasma levels in CP were significantly decreased at I h (P < 0.01)

and 4 h (P < 0.001) compared to pre-stimulatory levels and controls, and

a variance analysis showed significantly (P < 0.001) lower

post-stimulatory levels at 1 h and 4 h both in CP and in controls.

Alcohol consumption (40 g), however, did not influence plasma levels of

TGF-1beta, IGF-I or IGFBP-3 in either of the two groups at the time

frame applied. CONCLUSIONS: Acute alcohol intake induces a rise in the

plasma levels of IL-6 in CP as compared to controls. The low circulating

concentrations of MCP-1 1 and 4 h following alcohol consumption might

possibly reflect that this mediator acts locally via autocrine

mechanisms.

Publication Types: * Research Support, Non-U.S. Gov't

PMID: 15074399 [PubMed - indexed for MEDLINE]

8: Alcohol Clin Exp Res. 2003 Nov;27(11):1838-45.

Alcohol-induced suppression of lung chemokine production and the host

defense response to Streptococcus pneumoniae.

Boé DM, S, Zhang P, Quinton L, Bagby GJ. Department of

Physiology, Alcohol Research Center, Louisianna State University Health

Sciences Center, New Orleans 70112, USA.

BACKGROUND: Acute alcohol intoxication impairs neutrophil migration

in response to intrapulmonary infection with Streptococcus pneumoniae,

the most common bacterial cause of pneumonia. Many of the same host

defense functions that are impaired in the alcohol-intoxicated host are

mechanistically associated with chemokines, a group of proinflammatory

molecules that enhance neutrophil adhesion and direct neutrophil

migration to sites of inflammation. The purpose of this study was to

determine whether alcohol-induced chemokine suppression is responsible

for impaired neutrophil recruitment into the lung during infection of

the alcohol-intoxicated host. METHODS: S. pneumoniae was administered

(107 colony-forming units) intratracheally 30 min after intraperitoneal

injection of 20% alcohol (5.5 g/kg) or saline. Four hours after

bacterial challenge, bronchoalveolar lavage fluid (BALF) was collected,

and the ability of BALF to induce neutrophil chemotaxis and adhesion

molecule expression was measured by using chemotactic and flow

cytometric assays. In another experiment, intratracheal challenge was

performed by using recombinant macrophage inflammatory protein-2

(MIP-2), and BALF neutrophils were measured. RESULTS: BALF MIP-2 and

cytokine-induced neutrophil chemoattractant were decreased by alcohol,

and BALF from alcohol-intoxicated animals had decreased chemotactic

activity for neutrophils, as well as a decreased ability to up-regulate

neutrophil adhesion molecule expression, compared with controls. This

decreased chemotactic activity was significantly increased in the

alcohol group by repletion of chemokines to control levels. Alcohol also

suppressed neutrophil recruitment after intrapulmonary challenge with

MIP-2, suggesting that mechanisms other than chemokine suppression

contribute to the alcohol-induced effect. CONCLUSIONS: At least two

mechanisms, suppressed chemokine production and impaired neutrophil

adhesion molecule expression, likely work in concert in the

alcohol-intoxicated host to impair neutrophil adhesion and migration

into the lung during pneumococcal infection. These alterations in

neutrophil function likely increase the susceptibility of

alcohol-consuming hosts to pneumonia.

Publication Types: * Comparative Stu* Research Support, U.S.

Gov't, P.H.S. PMID: 14634502 [PubMed - indexed for MEDLINE]

9: J Infect Dis. 2001 Nov 1;184(9):1134-42. Epub 2001 Sep 20.

Acute ethanol intoxication suppresses lung chemokine production

following infection with Streptococcus pneumoniae.

Boé DM, S, Zhang P, Bagby GJ.

Department of Physiology, Section of Pulmonary and Critical Care

Medicine, Louisiana State University Health Sciences Center, New

Orleans, LA 70112, USA.

Alcohol intoxication impairs neutrophil function and increases host

susceptibility to Streptococcus pneumoniae. In a rat model of pneumonia,

the effects of acute intoxication were monitored for lung chemokine

responses, neutrophil recruitment, and bactericidal activity. Alcohol

delayed lung neutrophil recruitment, increased bacterial burden, and

decreased survival. Before neutrophil recruitment, bronchoalveolar

lavage (BAL) macrophage inflammatory protein-2 (MIP-2) and

cytokine-induced neutrophil chemoattractant (CINC) were decreased by

alcohol. This alcohol-induced effect was reversed at 6 h, when there

were large numbers of neutrophils in control BAL fluid, compared with

the alcohol-treated group. Cyclophosphamide-induced neutropenia

decreased neutrophil recruitment, minimizing the effects of recruited

neutrophils on chemokine levels, and extended the alcohol-induced

chemokine suppression. MIP-2 and CINC mRNA contents also were suppressed

by alcohol 4 and 6 h after infection. Thus, alcohol suppresses lung

chemokine activity in response to S. pneumoniae, which is associated

with delayed neutrophil delivery, elevated bacterial burden, and

increased mortality.

Publication Types: * Research Support, U.S. Gov't, P.H.S.

PMID: 11598836 [PubMed - indexed for MEDLINE]