Opium-related compounds, or 'opioids', have been used as painkillers for centuries. However, as well as being highly addictive, opioids, doctors have observed, can somehow affect the functioning of the immune system.
Now Yufang Shi and colleagues of the American Red Cross, Rockville, Maryland may have discovered how. Shi's group report in Nature that morphine can stimulate some cells to kill themselves. It does this by encouraging them to manufacture, or 'express', a protein, 'Fas', which they display on their surfaces. But Fas is no harmless artefact. Quite the contrary, Fas is the cellular version of the white flag of surrender. For, once Fas appears on the outside of a cell, another protein, 'Fas Ligand' (FasL) locks onto it, triggering the death of that cell.
Morphine can induce cell suicide (so-called 'apoptosis') only in cells to which it can actually affix - cells, that is, with opioid receptors. The two best-characterised groups of such cells are brain cells (neurons) and certain white blood cells (lymphocytes - a key part of the immune system.) Indeed Shi's team found that morphine induced a dramatic increase in the expression of Fas in fresh human lymphocytes - a phenomenon that could be prevented by blocking the opioid receptors.
In addition the researchers proved that the protein Fas is an essential piece of the cell-suicide jigsaw by showing that morphine did not promote apoptosis in white cells taken from Fas-deficient mice. They also proved that it is the interaction of Fas with its complementary protein, FasL, that induces cell death, by administering another Fas-binding substance, 'FasIg' to normal mice at the same time as the morphine. As predicted, FasIg prevented cell suicide by hooking onto Fas, thereby stopping FasL from doing likewise. Morphine sulphate alone, on the other hand, reduced the number of splenocytes (spleen white cells) in normal mice by 30% in 24 hours.
Under normal circumstances Shi's group explain "only a small portion of cells undergo opioid-induced apoptosis because Fas-mediated apoptosis requires FasL, which is expressed in only a limited number of cells." But during illness or injury, they suggest, "the amount of FasL may increase [and thus] opioid-induced apoptosis could also increase."
So, given that opioid-receptors are found mainly in brain and the immune cells, this is a discovery which not only bears on the consequences of taking morphine but that, as the researchers conclude, "should also help our understanding of the interaction between the nervous and the immune systems."
