Psoriasis support - Turning off the IL-10

Author

Turning off the IL-10

JXStern

2006-10-10, 4:27 pm

http://www.newscientist.com/article...er-viruses.html

Inflammation 'turned on' to fight killer viruses
13:01 10 October 2006
NewScientist.com news service
Debora MacKenzie

Researchers have cured viral meningitis in mice by blocking the action
of an anti-inflammatory immune molecule. The technique may one day
lead to cures in humans for hepatitis C and other chronic viral
infections, including meningitis and HIV.

Researchers have studied viral infections in mice and discovered that
in chronic infections – where a virus lingers in the body – the
rodents’ natural anti-inflammatory response effectively prevents its
immune system from attacking the virus.

Matthias von Herrath and colleagues at the La Jolla Institute for
Allergy and Immunology in California, US, studied an acute and chronic
meningitis infection in mice, called lymphocytic choriomeningitis
virus (LCMV). They discovered that mice with chronic infections had
high levels of the inflammatory-damping chemical interleukin-10
(IL-10).

When they gave mice with chronic LCMV a drug that blocks the
inflammatory-calming action of IL-10, the inflammatory immune response
was re-activated. Within a week the mice were healthier. In two weeks,
they had cleared the virus completely.

....

Many chronic viral infections in humans also elicit high levels of
IL-10, including cytomegalovirus, HIV, and hepatitis C. The latter
infects 180 million people worldwide – 3% of the total population –
and causes liver cirrhosis and cancer. Blocking IL-10 might allow such
people to clear these viruses, the researchers hope.

....

randall

2006-10-10, 4:27 pm

On Oct 10, 8:41 am, JXStern <JXSternChange...@gte.net> wrote:
> http://www.newscientist.com/article...turned-on-to...
>
> Inflammation 'turned on' to fight killer viruses
> 13:01 10 October 2006
> NewScientist.com news service
> Debora MacKenzie
>

<sniP>

And found in the last paragraphs,

"We are very excited about this," von Herrath told New Scientist.
There is always a risk that turning inflammation back on might lead to
excessive immune reactions, especially auto-immunity, where the body
attacks itself, he cautions. So they plan to first study the blood of
infected people to see if the antibody that blocks IL-10 will alter the
balance of immune cells.

Then perhaps it will be possible to treat people, perhaps alongside
other anti-viral treatments, such as vaccines. The US pharmaceutical
firm Schering-Plough, which owns the antibody, is already testing it in
humans against cancer, another disease where IL-10 may be damping more
immunity than is good for us.

Von Herrath thinks IL-10 may have evolved as a protective mechanism:
allowing us to live for a few decades with a chronic infection, rather
than being killed by a very strong autoimmune response.

----------------------------------

And it's that protective mechanism we need to control psoriasis if we
are going to the source of our genetic problems. Well, some of us
anyway.

How many times have we dealt with this?

http://groups-beta.google.com/group...oriasis&q=il-10

Only 120 hits? Are we sliPPing? LOL

You do get credit for putting it in a subject line.

And since you can find this abstract in the third thread (Is zinc an
essential mineral for psoriasis),

http://www.ncbi.nlm.nih.gov/entrez/...7&dopt=Abstract

Interleukin-10 promoter polymorphism IL10.G and familial early onset
psoriasis.

Hensen P, Asadullah K, Windemuth C, Ruschendorf F, Huffmeier U, Stander
M, Schmitt-Egenolf M, Wienker TF, Reis A, Traupe H.

Department of Dermatology, university of Munster, Munster, Germany.

BACKGROUND: The anti-inflammatory cytokine interleukin (IL)-10 is
considered to play a major role in the pathophysiology of psoriasis,
which is characterized by an IL-10 deficiency. Systemic administration
of IL-10 has been shown to be an effective therapy for psoriasis. The
IL-10 promoter region contains a highly polymorphic microsatellite
(IL10.G) and in a recent case-control study the IL10.G13 (144 bp)
allele was found to be associated with familial early onset psoriasis
(type 1 psoriasis) having a susceptible effect. OBJECTIVES: As it is
essential in multifactorial diseases to replicate findings before
definite conclusions can be drawn, we decided to perform a follow-up
study and to follow a genetic approach analysing allele transmission in
families with a positive family history of psoriasis. METHODS: We
studied 137 nuclear families (trio-design) comprising 456 individuals
and genotyped the IL10.G marker. For comparison we also genotyped the
microsatellite tn62 as a reference marker of the major psoriasis
susceptibility locus on chromosome 6p21 (PSORS1). In the present study
allele transmission was evaluated using the family-based association
test (FBAT) and GENEHUNTER 2.0 based on the transmission/disequilibrium
test. RESULTS: The G13 allele (144 bp) had a frequency of 24%, was
present in 88 families and clearly showed an even transmission (FBAT, P
= 0.753). In contrast, allele 3 (IL10.G9) (136 bp) had a frequency of
39%, was present in 110 families and was transmitted in 43 trios and
remained untransmitted in 67 trios (FBAT, P = 0.026), thus showing
preferential nontransmission. For the HLA-linked tn62-marker we
obtained a P-value of 0.00027 for allele 4 in the same study group.
CONCLUSIONS: In conclusion, we failed to confirm the susceptible effect
of the G13 allele, but provide the first data for a protective effect
of allele 3 (IL10.G9) for familial psoriasis. Our results suggest that
the IL10.G polymorphism is not a major locus, but acts as a minor
locus.

PMID: 12932247

Certainly a big clue for those able to lower severity via uPregulation
of IL-10. But for all others the conclusions reached here leaves them
with the YMMV dilemma.

Taking us back to multifactorial musings,
http://groups-beta.google.com/group...=multifactorial

randall..

randall

2006-10-10, 4:27 pm

Hi,

Can we do a test here with guava? This could be benefical if your
fighting cancer.

I'm betting for increased P severity though.

http://www.thetidenews.com/article....rTitle=3DGuava=
%20against%20cancer,%20high%20BP&qrColumn=3DKALEIDOSCOPE

Guava against cancer, high BP
=B7 Sunday, Sep 10, 2006

Although phytochemical studies identify more than 20 compounds in guava
extracts, the main constituents of its leaves are b-sitosterol,
maslinic acid, essential oils, triterpeniods and flavourniods.

Seo N et al of the Department of Dematology, Hamamastu University
School of Medicine, Japan, in a study entitled 'Anti-allergic Psidium
guajava extracts exert an antitumor effect by inhibition of T
regulatory cells and resultant augmentation of Th1 cells" showed how
the icnusin of guava extracts blocked IL -10-mediated, in vitro
induction of T regulatory (Tr) cells from CD4+ splenocytes of CT5/BL/6
mice, whereas the extracts exerted only a weak or no effect on the
development of Th 1 and Th 2 cells.

(For p we need more T-regs and what is icnusin?)

Accordingly, Tr cells were not induced from splenocytes of mice
administered orally with the extracts. Th1 popularisation is one of the
mechanisms underlying the therapeutic effects of herbal medicine.

Moreover, the extracts moved the Th1/Th2 balance to a Th1 dominant
status by directly attenuating Tr cells activity. In a study of tumor
immunity, mice pre-treated with the extracts exhibited retarded growth
of S.C. inoculated B/6 melanoma cells.

These findings recently published in Pub/Med suggest that guava
extracts are efficacious for the prevention of tumuor growth by
depressing Tr cells and subsequently shifting to Th 1 cells.

Dr. Osmand Onyeka, a consultant in National Health, disclosed to The
Tide on Sunday that Guava can improve one's health in three ways,
"Guava can improve your heart health by helping to control your blood
pressure and cholesterol," he said. "Guavas ability to lower blood
pressure could be the result of potassium. The mineral is an
electrolyte that is essential to electrical reaction in your body,
including your heart. It also keeps your heartbeat steady, and it
assists your kidneys in removing waste from your body,' continued
Onyeka.

In a study, researchers gave guava fruits to people with high blood
pressure before meats for 12 weeks. At the finish of the study, average
systolic (top number) blood pressured dropped by eight points and
diastolic (bottom number) fell by nine points.

Moreover, the study participants' total cholesterol dropped almost 10
per cent. Experts believe guava cholesterol lowering effect may be
connected with its useful soluble fibre content. Soluble fibre softens
and forms a gel that binds cholesterol and conveys it out of the body.

Guava against cancer growth high BP

According to Dr. Onyeka, the vitamin found in guava might be a
particularly effective antioxant against heart disease. Researches show
it raises good HDL cholesterol, and it helps prevent bad LOL
cholesterol from becoming oxidized and turning into artery clogging
plagues. Vitamin C. can also help keep your small vessels springy and
healthy.

Guava is a good source of lycopene. This carotenoid which gives many
plant foods their red or pink colouring, may help eradicate cancer, on
boost cardiac health. The evidence for lycopenes cancer-protective
effect is strongest for prostate cancer, lung cancer and stomach
cancer.

Although tomato and tomato-based products are major source of lycopene,
yet the guava enjoys much advantage as the Vitamin C component it
contains also protects consumers against cancer as against the tomato
and tomato-based products are linked with cancer. Further studies
suggest that a high consumption of Vitamin C reduces the risk of
developing, stomach, colon, breast and long cancers.

A Chinese folklore link guava with the treatment of diabetes for a very
long time. Even today, recent survey indicates that it can lower blood
sugar, though its effect is not as high as cholorpropamide and
metformin, drugs commonly used to lower blood sugar. Nevertheless, it
may be a natural way to curb diabetes.

According to Onyeka, the fruit of the guava may be tasty and
nutritious, but the leaves have been used as medicine for centuries.
Natives of the areas where guava grows use the leaves for digestive
problems, particularly diarrhea. They also put the crushed leaves on
wound and chew the leaves to relief toothaches. Although most of these
folk remedies have little scientific evidence to back them up, one
research did prove that there might be some elements of truth to the
anti diarrhea effect of guava leaves.

Also, its leaves and barks are decocted by the Tikuna Indians as a cure
for diarrhea. This has been used by many tribes through Amazon, in
addition to curing dycentary and sore threats, vomiting, stomach
upsets, for vertigo, and to regulate menstrual periods.

Tender leaves of guava are chewed for bleeding gum and bad breath, and
it is proved to prevent hangover (if chewed before drinking). It is
also used by the Indians as a douche for vaginal discharge and to
tighten and tone vaginal walls after child birth.

A decoction of the bark and/or leaves or a flower infusion is used for
curing wounds, ulcers, skin sores. Flowers are also mashed and applied
to painful eye conditions like sun strain, eye injury or
conjunctivitis.

Though the guava fruit may be seen simple, yet it medicinal and medical
purposes are worth admiring. You too can benefit from the catalogue of
the guava potentials.

------------------

The b-sitosterol is estrogenic and may be the main culprit,
http://www.ncbi.nlm.nih.gov/entrez/...=3DRetrieve&do=
pt=3DAbstractPlus&list_uids=3D14615068&query_hl=3D11&itool=3Dpubmed_docsum

-------------------------------------------

If I had cancer i'd be sucking those guava's down left and right. lol

So what is it for P? In cancer we know your skewed towards the Th2
side.

Yet for psoriatics that have the Th1 skew there must be other factors
and genes to pin this thing on.

I wonder if my gut/lps theory still holds up?

YeP!

http://ajp.amjpathol.org/cgi/conten...ract/169/4/1223
Posttranslationally Modified Proteins as Mediators of Sustained
Intestinal Inflammation

<sniP>

Oxidative and carbonyl stress leads to generation of
N{epsilon}-carboxymethyllysine-modified proteins (CML-mps), which are
known to bind the receptor for advanced glycation end products (RAGE)
and induce nuclear factor (NF)-{kappa}B-dependent proinflammatory gene
expression. To determine the impact of CML-mps in vivo, RAGE-dependent
sustained NF-{kappa}B activation was studied in resection gut specimens
from patients with inflammatory bowel disease. Inflamed gut biopsy
tissue demonstrated a significant up-regulation of RAGE and increased
NF-{kappa}B activation. Protein extracts from the inflamed zones, but
not from noninflamed resection borders, caused perpetuated NF-{kappa}B
activation in cultured endothelial cells, which was mediated by CML-mps
including CML-modified S100 proteins. The resulting NF-{kappa}B
activation, lasting 5 days, was primarily inhibited by either depletion
of CML-mps or by the addition of sRAGE, p44/42 and p38
MAPKinase-specific inhibitors. Consistently, CML-mps isolated from
inflamed gut areas and rectally applied into mice caused NF-{kappa}B
activation, increased proinflammatory gene expression, and
histologically detectable inflammation in wild-type mice, but not in
RAGE-/- mice. A comparable up-regulation of NF-{kappa}B and
inflammation on rectal application of CML-mps was observed in
IL-10-/- mice. Thus, CML-mps generated in inflammatory lesions have
the capacity to elicit a RAGE-dependent intestinal inflammatory
response.

----------------------------------------

A gene in the gut or uP or downstream that triggers one in the liver?
The skin? both?

Or simply a leaky gut (permeable) and a genetic problem with endotoxin
leakage? And a dozen or more
genes to keep it all very flaky?

randall...not enough flaky genes to pin it on or to many?