Brain and immunity: mapping the link.

Brain and immunity: Mapping the link

New research shows that opiate drugs, such as morphine, act on a brain region that dampens the ability of natural killer cells to destroy cancer and viral-infected cells. The finding may eventually help explain why heroin addicts and people under stress have suppressed immune systems.

Richard J. Weber of the National Institute of Diabetes and Digestive and Kidney Diseases and Agu Pert of the National Institute of Mental Health picked six brain regions where opiate drugs act as likely candidates for immune system regulation. They injected six groups of male rats with enough morphine to make them drowsy -- 6.6 nanomoles directed into one of the six regions to be tested. A seventh group of control rats got no morphine.

Three hours after morphine injection, the researchers harvested killer cells taken from the rats' spleens, mixed them with cancer cells and measured the killer cells' ability to destroy their tumor targets. Weber and Pert found a "dramatic" drop in killer cell performance when rats got morphine delivered to a brain region known as the peri-aqueductal gray matter of the mesencephalon (PAG). Rats in the PAG group showed a 63 percent drop in their natural killer cell activity as compared with controls, the researchers report in the July 14 SCIENCE. Rats receiving morphine injections in other brain areas showed no decline in killer cell activity when compared with controls.

John C. Liebeskind, a psychologist at the University of California, Los Angeles, calls the report an "important contribution." Liebeskind's research team first demonstrated in 1986 that morphine acts on the brain to suppress natural killer cell activity, but that report did not pinpoint the site of action. The evidence implicating the PAG region is not surprising, Weber says, noting that past research on animals showed that electric shocks delivered to the PAG spur cancerous tumor growth.

The new report suggests PAG's involvement in the immune suppression seen among people addicted to heroin. (Both morphine and heroin are derived from opium.) Scientists have long observed that opiate addicts have malfunctioning immune systems that leave them prey to infection. Weber and Pert's study suggests heroin may bind to opiate receptors in the PAG region to somehow produce sluggish killer cells.

The PAG area also may play a role in the immune suppression seen in people under a lot of stress, Weber says. His study hints that morphine-like substances released by PAG neurons may suppress immune function just as morphine reduces killer cell activity in the rat model. The body produces these natural painkillers in times of stress, perhaps compromising the immune system as an unwanted side effect. That theory remains highly speculative, but Weber's laboratory plans further research to elucidate the PAG-immunity link.