Immunomodulatory effects of opioids

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Opioids have been shown to modulate the immune system in animal models by affecting both the acquired and innate arms of the immune system. Many of these effects are reversed by opioid antagonists. Opioids have also been shown to induce sepsis in laboratory animals. Opioid administration alters immune parameters in healthy humans at analgesic doses and may increase the risk of infection in some patient populations. OP3 receptor agonists, like morphine are likely to cause immunosuppression, while OP3 receptor partial agonist buprenorphine and OP3 receptor antagonist naloxone appear to confer protective effects on the immune system. Acute lung injury is a significant cause of mortality in the United States and patients with lung injury are commonly treated with opioids. The effect of opioids on sepsis induced acute lung injury has not been described and this project evaluated this effect. The hypothesis was that rats treated with morphine will have a worse outcome than rats treated with buprenorphine and naloxone. Acute lung injury was induced in rodents using the cecal ligation and puncture technique. Injections of morphine, buprenorphine, naloxone and saline were administered subcutaneously every eight hours for 4 days. Specific immune parameters were evaluated after the rats were euthanized on day 5. Evaluation of the data obtained revealed that rats treated with morphine had a better survival rate, contrary to the hypothesis of the study. This effect is likely related to the benefit of adequate analgesia. The study also revealed that the rats treated with naloxone had a worse outcome, which was again contrary to the hypothesis of the study and may indicate that naloxone might actually be immunosuppressive in cases of sepsis induced acute lung injury. This study and subsequent studies carry very important socioeconomic consequences since opioids are the most widely used analgesic drugs in human and veterinary medicine. Further studies need to be performed to better characterize the effect of opioids on lung injury.