Is immunomodulation by opioid drugs of clinical relevance?

There has been a growing interest in elucidating the immune consequences of opioid administration for the management of pain. Several studies in vitro and in vivo have demonstrated an immunomodulating effect of opioids. The neuro-endocrine interactions observed after opioid application contribute to this effect as well as direct alterations of immune effector cells. Opioid-induced immunomodulation is mediated by opioid receptors found on immunocytes and in the central nervous system. This review will elucidate the molecular mechanisms of central and peripheral immunomodulation by opioids with special emphasis on the clinical significance of these findings.

Recent research has focused on the cellular signaling cascades associated with opioid receptor activation. The crosstalk between chemokine and opioid receptors on leukocytes has opened new insights into the molecular mechanisms involved in opioid-induced immunomodulation. Heterologous desensitization and phosphorylation of chemokine receptors by opioids may not only mediate the immunosuppressive effects of opioids but may also modulate the perception of pain.

Although immunomodulating effects of opioids are well established, a final statement regarding the clinical relevance cannot be made, since the existing clinical and experimental data are preliminary and inconclusive. Therefore, further clinical studies are mandatory to elucidate the influence of opioid treatment on immune regulation in different clinical settings. Further investigations may help to provide sufficient analgesia by application of opioids, as well as assessing the advantages and disadvantages on immune function.