Welcome to the first edition
of the Alchemist Lab newsletter.
I will start with a brief summary
of the information to be presented.
Th1 & Th2 are types of T helper cells. They produce
cytokines,
which are small secreted proteins which regulate immune
function,
inflammation, and red blood cell production. A brilliant
study out
of the La Jolla Institute for Allergy & Immunology
found that they
were able to eliminate chronic viral infections, including HCV in
mice by blocking IL10. IL10 is an interleukin which is a type of
cytokine that is made by white blood cells and acts on other white
blood cells. IL10 is produced by Th2. Hepatitis C causes the body
to produce more IL10 than any other chronic infection. Oxymatrine
upregulates Th1 and lessens Th2. Gamma interferon is the principle
cytokine produced by Th1. Glutathione depletion also leads to Th2
dominance. Glutathione is the principal anti-oxidant found
intracellularly in the liver.
The next edition will compile patient results using Oxymatrine.
A major finding that could lead to a new approach for treating
hepatitis C and other chronic virus infections was announced today
by researchers at the La Jolla Institute for Allergy & Immunology
(LIAI). The research team, using controlled laboratory studies of
mice, was able to eliminate a chronic virus infection in the
animals by blocking a key messenger molecule in the immune system.
The finding has particular relevance for hepatitis C, a viral
illness which can cause liver disease and cancer, but may also be
applicable to AIDS, cytomegalovirus and other chronic virus
infections.
"This is a significant advance that holds great promise for the
treatment of chronic virus infections," said Mitchell Kronenberg,
LIAI President & Scientific Director. He noted that the research
is
particularly exciting because the scientific team was able to
completely eradicate the usually chronic infection in the mice, not
just tone it down, like many of the current treatment methods for
such infections.
The research team, led by Matthias von Herrath, M.D., announced its
finding in a paper, "Resolution of a Chronic Viral Infection
Following IL-10 Receptor Blockade," published today in the online
version of the Journal of Experimental Medicine. A separate study,
led by Michael Oldstone from the Scripps Research Institute,
produced similar results and was published Sunday in a science
journal.
LIAI's research team used a novel method for tackling a chronic
viral infection, which involved releasing the disease-fighting
power of the immune system by blocking the interleukin-10 (IL-10)
messenger molecule receptor with a simple antibody. Normally, this
molecule, which is produced at substantial levels during hepatitis
C, HIV and cytomegalovirus infections, acts to suppress the immune
system's attack on chronic virus infections. "We thought, 'what if
we try to correct what the immune system seems to be doing wrong in
response to many chronic viral infections?,'" said von Herrath. "So
we unleashed the power of the immune system by using an antibody to
block the IL-10 receptor. This taught the immune system to take the
right action and fight the disease."
The discovery by scientific researchers that mice chronically
infected with lymphocytic choriomeningitis virus produce large
amounts of IL-10 led to the development of this new intervention.
Von Herrath used a version of the virus that causes chronic
infections in a study involving 40 infected mice. The mice were
treated with the IL-10-blocking antibody for two weeks. "They got
better after one week," he said. "After two weeks, the infection
was resolved in the majority of the mice and, in the end, all
animals were able to cope with the virus. They developed a normal
antiviral immune response, gained weight and returned to a healthy
state." Von Herrath noted that their studies showed that the
treatment worked best when given immediately after infection. "The
later you give it after the infection, the lesser the efficacy," he
said.
Von Herrath said that future studies in humans should primarily
target hepatitis C because it causes the body to produce the most
IL-10 of any of the chronic virus infections. Hepatitis C has been
compared to a "viral time bomb." The World Health Organization
estimates that about 180 million people, some 3% of the world's
population, are infected with hepatitis C virus, 130 million of
whom are chronic carriers at risk of developing liver cirrhosis
and/or liver cancer. The hepatitis C virus is responsible for
50-76% of all liver cancer cases, and two thirds of all liver
transplants in the developed world. Current estimates in the U.S.
are that 3.9 million Americans are chronically infected with
hepatitis C.
Currently, hepatitis C is treated with a variety of drugs, with
only modest success. "The problem is you need to strengthen the
immune system to fight the (chronic) virus, but in doing so it may
destroy too many cells. This cellular damage can eventually become
intolerable for the body," Von Herrath explained, a condition known
as immunopathology. However, in their studies with IL-10, "we found
that by blocking this molecule, you can release the brakes on the
immune system at a crucial juncture," he said. "This results
in an
immune system attack that is intense enough to rid the body of the
disease, but not so high as to cause immunopathology."
Von Herrath said the research team will continue to expand on the
finding. "One of the next steps will be to test the IL-10 blocking
antibody on human cells in the lab to see whether these cells also
become normal and functional against the virus and to test
combination therapies that add viral vaccines, anti-viral drugs and
other antibodies to the IL-10 receptor blockade. Combination
therapies bear the promise to minimize potential side effects while
achieving synergy in combating the viral disease."
Now with this research in mind we will go to PubMed, which is where
the NIH and the National Library catalogue medical research on the
web. This is a study trying to illuminate why Oxymatrine is
effective in treating Hepatitis B. If it is difficult to follow
just bear in mind the conclusion it draws.
Department of Infectious Disease, Peking University First Hospital,
Beijing 100034, China.
OBJECTIVE: To explore the effects of oxymatrine on serum levels of
Th1/Th2 cytokines in HBsAg transgenic mice. METHODS: HBsAg
transgenic mice were divided into oxymatrine group and control
group. Each mouse was injected with either oxymatrine 200 mg/kg 0.2
ml or 0.9% NaCl 0.2 ml intraperitoneally once a day for 30 days.
Serum IFN-gamma, IL-2 and IL-4, IL-10 were quantitated before and
after different treatment. RESULTS: There was no significant
difference on the levels of IFN-gamma and IL-4 before and after
treatment in control group. While in oxymatrine group, the levels
of IFN-gamma before and after treatment were (3.108+/-3.172) pg/ml
and (11.059+/-6.971) pg/ml; those of IL-4 were (29.045+/-13.235)
pg/ml and (13.024+/-9.002) pg/ml (both P less than 0.001). After
treatment, the levels of IL-2 in control and oxymatrine group were
(1.070+/-0.447) pg/ml and (5.537+/-2.887) pg/ml (P less than 0.000
1); and those of IL-10 were (97.226+/-73.306) pg/ml and
(33.607+/-23.154) pg/ml (P less than 0.01). CONCLUSION: After
injection of oxymatrine to HBsAg transgenic mice, the serum
concentration of Th1 cytokines increased while the Th2 cytokines
decreased. This helps us understand the anti-HBV effect of
oxymatrine.
Two sources worth noting for this newsletter are Medical News
Today, which has an excellent newsletter and published the La Jolla
study on IL10, and PubMed which is run by the NIH and catalogues
medical research on the web. Any feedback on the first edition we
would appreciate. For this edition we included the technical
medical language that researchers use that we normally re-write.
Steven Finkbine 10/31/2006
Alchemist Lab, LLC, P.O. Box 58, San Geronimo, CA 94963, USA
