Morphine Drives Immune Cells to Suicide

Opioids such as morphine, which have been used as painkillers for centuries, have long been known to tune down the immune system. In today's issue of Nature, immunologists explain how this may happen: Morphine, they say, predisposes immune cells to commit suicide. The result may help unravel the interplay between the brain and the immune system.

White blood cells, the immune system's watchdogs that attack invaders, are kept under tight scrutiny, lest they turn against cells of their own body and cause autoimmune diseases. One mechanism to dispose of them if they do go on the rampage is to induce them to kill themselves. This suicidal cascade, known as apoptosis, is kicked off when a protein on the cells' surface called Fas meets another molecule, Fas ligand or FasL, and the two bind. Immunologist Yufang Shi of the Holland Laboratory of the American Red Cross in Rockville, Maryland, suspected that Fas could also be involved in the immune suppression caused by opioids.

Shi and his team measured the number of Fas proteins on the surface of white blood cells before and after exposing them to morphine. They discovered that morphine sharply increased Fas density on the cells' surfaces. This makes the cells much more susceptible to apoptosis whenever FasL is around, and when Shi added FasL to the cell cultures, the morphine-treated cells started dying immediately, while untreated cells stayed alive. In another experiment, Shi injected mice with morphine and found that after 24 hours the number of cells in their spleens--one of the immune system's centers--had dropped by about 30%.

Scientists know that the brain, too, produces its opioids. The newly discovered effect of morphine on blood cells, says Shi, suggests that opioids may be chemical messengers between the brain and the immune system. Immunologist Douglas Green of the La Jolla Institute for Allergy and Immunology agrees: "It's a provocative finding." But others caution against overinterpretation of the study. Externally administered painkillers may have a totally different effect from the brain's natural opioids, says Toby Eisenstein, an immunologist at Temple University School of Medicine in Philadelphia. Whereas the first suppresses the immune system, "there are a great deal of studies that suggest that endogenous opioids are actually immunostimulatory."