"We provide clear evidence that DIM is effective in augmenting the
immune response for the mice in the study, and we know that the immune
system is important in defending the body against infections of many
kinds and cancer," said Leonard Bjeldanes, UC Berkeley professor of
toxicology and principal investigator of the study. "This finding
bodes well for DIM as a protective agent against major human maladies."
Previous studies led by Bjeldanes and Gary Firestone, UC Berkeley
professor of molecular and cell biology, have shown that DIM halts the
division of breast cancer cells and inhibits testosterone, the male
hormone needed for growth of prostate cancer cells.
In the new study, the researchers found increased blood levels of
cytokines, proteins which help regulate the cells of the immune system,
in mice that had been fed solutions containing doses of DIM at a
concentration of 30 milligrams per kilogram. Specifically, DIM led to
a jump in levels of four types of cytokines: interleukin 6,
granulocyte colony-stimulating factor, interleukin 12 and
interferon-gamma.
"As far as we know, this is the first report to show an immune
stimulating effect for DIM," said study lead author Ling Xue, who was
a Ph.D. student in Bjeldanes' lab at the time of the study and is now
a post-doctoral researcher in molecular and cell biology at UC
Berkeley.
In cell cultures, the researchers also found that, compared with a
control sample, a 10 micromolar dose of DIM doubled the number of
white blood cells, or lymphocytes, which help the body fight
infections by killing or engulfing pathogens. (A large plateful of
broccoli can yield a 5-10 micromolar dose of DIM)
When DIM was combined with other agents known to induce the
proliferation of lymphocytes, the effects were even greater than any
one agent acting alone, with a three- to sixfold increase in the
number of white blood cells in the culture.
"It is well-known that the immune system can seek out and destroy
tumor cells, and even prevent tumor growth," said Xue. "An important
type of T cell, called a T killer cell, can directly kill certain
tumor cells, virally infected cells and sometimes parasites. This
study provides strong evidence that could help explain how DIM blocks
tumor growth in animals."
DIM was also able to induce higher levels of reactive oxygen species
(ROS), substances which must be released by macrophages in order to
kill some types of bacteria as well as tumor cells. The induction of
ROS - three times that of a control culture - after DIM was added to
the cell culture signaled the activation of macrophages, the
researchers said.
"The effects of DIM were transient, with cytokine and lymphocyte
levels going up and then down, which is what you'd expect with an
immune response," said Bjeldanes. "Interestingly, to obtain the
effects on the immune response, DIM must be given orally, not injected.
It could be that the metabolism of the compound changes when it is
injected instead of eaten."
To examine the anti-viral properties of DIM, the researchers infected
mice with reoviruses, which live in the intestines but are not
life-threatening. Mice that had been given oral doses of DIM were
significantly more efficient in clearing the virus from their gut - as
measured by the level of viruses excreted in their feces - than mice
that had not been fed DIM.
"This means that DIM is augmenting the body's ability to defend itself
by inhibiting the proliferation of the virus," said Bjeldanes. "Future
studies will determine whether DIM has similar effects on pathogenic
viruses and bacteria, including those that cause diarrhea."
The discovery of DIM's effects on the immune system helps bolster its
reputation as a formidable cancer-fighter, the researchers said. "This
study shows that there is a whole new universe of cancer regulation
related to DIM," said Firestone, who also co-authored the new study. "There
are virtually no other agents known that can both directly shut down
the growth of cancer cells and enhance the function of the immune
system at the same time."
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