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.
Materials provided by NIH/National Institute On Drug Abuse. Note: Content may be edited for style and length.
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