Opioid Therapy and Immunosuppression

Abstract

The idea that opioids modulate the immune system is not new. By the late 19th century, Cantacuzene, used morphine to suppress cellular immunity and lower the resistance of guinea pigs to bacterial infection. While exogenous opioids mediate immunosuppression, endogenous opiates exert opposite actions. Acute and chronic opioid administration is known to have inhibitory effects on humoral and cellular immune responses including antibody production, natural killer cell activity, cytokine expression, and phagocytic activity. Opiates behave like cytokines, modulating the immune response by interaction with their receptors in the central nervous system and in the periphery. Potential mechanisms by which central opiates modulate peripheral immune functions may involve both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. The presence of opioid receptors outside the central nervous system is increasingly recognized. Those receptors have been identified not only in peripheral nerves but also in immune inflammatory cells. The immunosuppression mediated by opiates may explain the increased incidence of infection in heroin addicts. Opiates may also promote immunodeficiency virus infection by decreasing the secretion of alpha and beta chemokines (important inhibitory cytokines for the expression of HIV) and at the same time increasing the expression of chemoreceptors CCR5 and CCR3, coreceptors for the virus. The fact that peripheral immunosupression is mediated at least in part by opioid receptors located in the central nervous system and that intrathecally administered opioids do not exert the same immunosuppressive effects may have important clinical implications for those patients receiving long-term opioid therapy for malignant and nonmalignant pain.

Role of Opioidergic System in Humoral Immune Response

“…Recently findings from several investigators (Quaglio et al, 2002;Nath et al, 2002;Georges et al, 1999;Vallejo et al, 2004;Roy et al, 2006;Somaini et al, 2008) support the role of opiates in suppressing a variety of immunological end points in opiate abusers. Endogenous opioids seem to have a physiological role in modulating the Th1/Th2 balance, by reducing Th1 and enhancing Th2 representative cytokines.…”

“…In this regard, available evidence shows that while morphine and heroin are liable to attenuate the immune response, long-acting opioids that are used in withdrawal treatment, such as methadone and buprenorphine, are largely devoid of immunosuppressive activity. Opioids can also influence the immune function through the activation of the descending pathways of the hypothalamus-pituitary axis (HPA) and the sympathetic nervous system (Vallejo et al, 2004). This review on role of opioidergic system in humoral immune response summarizes the effect of opiate receptor polymorphism on innate and adaptive immunity, identifies the role of the mu opioid receptor in these functions, and finally discusses how changes in these parameters may increase the risk for opportune infections in drug dependent subjects or attenuate the symptoms of rheumatoid arthritis.…”

Morphine and Heroin Differentially Modulate In Vivo Hippocampal LTP in Opiate-Dependent Rat

“…Heroin (3, 6-diacetylmorphine) was introduced in 1898 and was heralded as a more potent pain killer and remedy for morphine. However, the major pharmacological effects of heroin can be traced back to structural properties of the morphine molecule, and heroin shares a similar pharmacological profile with morphine: both induce analgesia, hypothermia, sedation, inhibition of intestinal motility, and depression of the immune function (Gutstein and Akil, 2001;Thronhill et al, 1976;O'Mahony et al, 2001;Petersen and Fujimoto, 1983;Ghodse and Reed, 1984;Manzanares et al, 1999;Vallejo et al, 2004;Weber et al, 2004).…”

Perioperative management and oncological outcomes following radical cystectomy for bladder cancer: a matched retrospective cohort study

“…Specifically, surgical manipulation disseminates malignant cells into the bloodstream, 4 surgical stress promotes metastatic growth by affecting immunosuppression through neuroendocrine pathways, 2,3 and the use of systemic opioids directly inhibits NK cell activity. [5][6][7][8][9] Finally, blood transfusion induces immunosuppression. 10 While systemic morphine reduces the NK cell activity, the addition of spinal blockade to general anesthesia in a murine model attenuated the propagation of metastases by surgery.…”