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| Cocaine use is known to have negative effects on the immune system but how the
drug exerts this effect is poorly understood. Now a research team, led by Dr.
Steven Dubinett from the university of California Los Angeles Lung Cancer
Research Program, has demonstrated that some of cocaine's effects on the immune
system may be mediated by sigma receptors. These receptors are unique proteins
found in the brain and other areas of the body and have been shown to play a
role in some of the toxic and behavioral effects of the drug.
The researchers administered cocaine or saline to male mice five times per
week. Another group of mice were given the sigma receptor antagonist BD1047--a
substance that blocks the sigma receptors and does not stimulate them--in
addition to cocaine or saline. After 2 weeks, tumor cells were implanted in the
mice. Tumor growth and interleukin (IL)-10 concentrations were measured. IL-10
is a chemical messenger that suppresses the production of several substances
that inhibit tumor growth. Tumors in cocaine-exposed mice were significantly
larger and contained higher levels of IL-10 than those in saline-treated mice.
However, tumor growth was less enhanced in mice who received both cocaine and
treatment with the sigma receptor antagonist BD1047. In addition, administration
of anti-IL-10 antibody reversed the tumor growth-promoting effects of sigma
ligand agonists--substances that bind to and stimulate the receptors--such as
cocaine.
In a separate study, the researchers administered cocaine or saline and the
sigma receptor antagonist BD1047 to male mice. Two weeks later, the mice were
administered staphylococcal entertoxin, which promotes IL-10 production by
immune cells. The researchers found that the level of IL-10 in the blood of
cocaine-exposed mice was significantly higher than those receiving saline but
IL-10 production was inhibited in mice who received the sigma receptor
antagonists.
WHAT IT MEANS: These finding suggest that cocaine and other drugs that stimulate
sigma receptors may promote tumor growth by increasing the production of
immunosuppressive chemical messengers. However, the researchers say that further
research is needed to determine whether cocaine causes cancer.
This study, cofunded by the National Institute on Drug Abuse, was published in
the April 1 issue of The Journal of Immunology.
This story has been adapted from a news release issued by NIH/National Institute
On Drug Abuse.
Alan
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