Pro-inflammatory cytokine modulation in response to chronic fentanyl self-administration in rats

Opioid abuse is associated with an increased prevalence of blood borne viruses and opportunistic infections due to specific immunomodulatory effects of opioid drugs that can influence this susceptibility. Fentanyl, a schedule II opioid, has gained prominence on the illicit market contributing to the rising number of opioid-related deaths, but little information is available regarding 1) the immune effects of fentanyl and 2) how chronic self-administration (SA) of fentanyl impacts central and systemic inflammation. In the current project, a rat model was used to examine the effects of voluntary chronic, long-access fentanyl SA on in vivo cytokine production in response to the endotoxin lipopolysaccharide (LPS). The specific cytokines of interest were IL-1β, TNF-α, and IL-6, which are the most prominent neuromodulatory cytokines associated with inflammation. Following 30 days of fentanyl SA, IL-1β and TNF-α levels (IL-6 data not yet available) were suppressed after 7 days of abstinence compared to Saline/SA control concentrations; this suppression recovered to that of Saline/SA control concentrations after 30 days of abstinence. The results of this study show for the first time that chronic fentanyl SA significantly suppresses the in vivo cytokine response to endotoxin challenge with possible implications for opioid relapse. Results also show for the first time that recovery from the expected opioid-mediated immunosuppression is possible after an extended period of abstinence.M.S.Includes bibliographical reference