Opioid G protein-coupled receptors: signals at the crossroads of inflammation

The analgesic property of opiates has been known since ancient times. Only recently has an appreciation of the broad effects of opioids on the inflammatory response emerged. Acting largely through mu-, kappa- and delta-opioid G protein-coupled receptors on T lymphocytes and macrophages, cognate ligands modulate many activities of these cells, including cytokine production. In addition to acting as chemotactic stimuli, opioids can, through the process of heterologous cross-desensitization, act as stop signals in leukocyte trafficking. When administered into the central nervous system, certain chemokines can cross-desensitize to the analgesic effect of opioids. We propose that opioids should be considered members of the cytokine family and that future research on opioids could yield new therapies for inflammatory and infectious diseases, including HIV-1 infection.