Immunosuppressive effcts of opioids

The immunosuppressive effects induced by opioid analgesics are thought to be significant modulators of the immune responses in patients with acute or chronic pain. There is now a substantial body of evidence demonstrating that opioids and endogenous opioid peptides modulate immune function. Moreover, inflammatory mediators have been shown to modify the release of opioid peptides from the immune system cells and also from cells of the peripheral and central nervous systems.

Some of the more profound consequences of opioid depressant effects are seen as increased susceptibility to bacterial and viral infection, lack of defences in cancer patients (evidenced by decreased survival and increased metastases) and an increased susceptibility to HIV infection in drug abusers.

Most opioids induce alterations in the biochemical and proliferative properties of the various cellular components of the immune system and the potential clinical effects of exogenously administered opioids on the immune system cannot be ignored. Patients with lymphoid organ atrophy, impaired natural killer cell function and a reduction in the immature-to-mature thymic lymphocyte ratio are, therefore, at risk from the effects of opioids, especially those patients who are, for whatever reason, immunocompromised.

In addition to these considerations, morphine (the 'gold standard') decreases the proliferation of stimulated human lymphocytes in a dose dependent manner, decreases T-cell rosette formation, decreses the total number of circulating lymphocytes and reduces the generation of IFN-alpha and IFN-beta, a naloxone reversible phenomenon. This effect is due mainly to a direct effect upon the mu-opioid receptor rather than through the indirect mechanism via corticosterone. A variety of projects have shown that the immunological effects of opioids are exerted via the mu-opioid recptor rather than any of the other opioid receptors. To avoid, as far as possible, opioid-induced deleterious effects, selecting for clinical use those opioids without significant immunosupression is not difficult. Structurally they are the opioids with a carbonyl substitution at C6 and a single bond between C7-8. Included in this group are buprenorphine, oxycodone and tramadol. The pharmacological properties of these agents are such that they could readily replace the immunosuppressive opioids in clinical use without any problems. In some cases, there would be other advantages as well as offering immunostability.