Therapeutic and Prophylactic Vaccines to Counteract Fentanyl Use Disorders and Toxicity.

The incidence of fatal overdoses has increased worldwide due to the widespread access to illicit fentanyl and its potent analogues. Vaccines offer a promising strategy to reduce the prevalence of opioid use disorders (OUDs) and to prevent toxicity from accidental and deliberate exposure to fentanyl and its derivatives. This study describes the development and characterization of vaccine formulations consisting of novel fentanyl-based haptens conjugated to carrier proteins. Vaccine efficacy was tested against opioid-induced behavior and toxicity in mice and rats challenged with fentanyl and its analogues. Prophylactic vaccination reduced fentanyl- and sufentanil-induced antinociception, respiratory depression, and bradycardia in mice and rats. Therapeutic vaccination also reduced fentanyl intravenous self-administration in rats. Because of their selectivity, vaccines did not interfere with the pharmacological effects of commonly used anesthetics nor with methadone, naloxone, oxycodone, or heroin. These preclinical data support the translation of vaccines as a viable strategy to counteract fentanyl use disorders and toxicity.

The effects of pre-emptive epidural sufentanil on human immune function.

BACKGROUND: Surgical stress and general anaesthesia suppress immune functions, including natural killer cell (NK) activity. This suppression could be attributed, at least in part, to the effect of opiates. METHODS: Twenty patients undergoing abdominal hysterectomy received epidural sufentanil (50 microg) either before (pre-emptive) or at the end (control group) of surgery. Post-operative pain relief was provided using sufentanil from a patient-controlled epidural analgesia (PCEA) system. Systemic immunity was assessed by determining leucocyte counts, NK cell counts and activity, lymphocyte response to mitogen stimulation, and secretion of pro-inflammatory cytokines. RESULTS: In the pre-emptive group there was a significant decrease in NK activity on the first and third post-operative day (P < 0.05) compared with baseline values and on the third postoperative day (P < 0.05) compared with the control group. The number of total leucocytes and neutrophiles increased in both groups post-operatively, but no differences were found in the levels of mononuclear lymphocyte populations or in their mitogen responses. Interleukin-6 (IL-6) concentration increased in both groups after the operation. In addition, at the end of the surgery the IL-6 level was greater in the control group than in the pre-emptive group. Interleukin-1 (IL-1) levels had decreased significantly at the end of surgery and 4 h later compared with baseline levels in the pre-emptive, but not in the control group. CONCLUSIONS: Pre-emptive epidural sufentanil during combined propofol and isoflurane anaesthesia had minor effects on the immune response after hysterectomy. The lower production of pro-inflammatory cytokines (IL-1, IL-6) in the pre-emptive group compared with the control group is beneficial, but its clinical importance remains to be determined.