Orthopedics Today, November 2013
Javad Parvizi, MD FRCS; Fatih Küçükdurmaz, MD

As if the numerous adverse effects of opiates on the human body were not enough, emerging evidence unravels a link between opioids and infection.

The link between opioids and infection was noted in the late 1980s during HIV research. Epidemiological studies demonstrated that the progression of HIV-1 infection was slower in patients who halted the abuse of opioid drugs. In numerous primate models of HIV infection, similar observations were made. The administration of opioids to these animals led to disruption of T-cell and polymorphonuclear-mediated immune function while exacerbating viral replication.

Since early 1990, when such observations were made, extensive mechanistic studies have been conducted, and the cellular mechanism by which opioids exert their adverse effect on HIV-infected patients has been largely unraveled. The effect of opioids on the immune cells is believed to be modulated via μ-receptors and regulated by c-AMP. Interestingly, it has been observed that the presence of opioids in the blood in concert with the HIV-1 protein exacerbates dysregulation of immune system and can lead to better survival of the infecting virus.

In recent years, evidence is emerging to implicate that opioids also affect the function of macrophages in addition to T-cells. Long-term use of opiates has been demonstrated to decrease the proliferative capacity of macrophage progenitor cells. As macrophages are an essential element of defense against infection, the adverse influence on the function of these cells can have far-reaching implications. These phagocytes, for their ability to engulf and clear organisms, present the first line of defense against microorganisms. The exact mechanism by which the function of lymphocytes and macrophages is adversely affected by opiates is being worked out. There are, however, studies showing that morphine affects the migratory capabilities and phagocytic function of macrophages, and exert this effect through Fcy receptors. In addition, morphine has been shown to increase the susceptibility to opportunistic infections by affecting macrophage function.

Thus, the link between opioids and infections includes those caused by bacteria and opportunistic organisms. Recent studies have shown that morphine induces bacterial translocation in mice by compromising intestinal barrier function. Morphine has been shown to potentiate the effect of Salmonella enteral infection through the μ-receptor. Spore-forming bacterial infections, including anthrax, are found to affect individuals abusing opioids with more frequency.

Thus, it is becoming clear that opioids — besides their numerous undesirable effects — are immunosuppressive agents resulting in an increased incidence of bacterial infections and more rapid progression of viral infections in those who are chronic users of these agents. The question that arises is whether opioids, still commonly administered in the postoperative period, can affect the migratory behavior of other cells such as fibroblasts and result in obtunded wound healing.