Abstract
The opioid antagonist naltrexone hydrochloride has been suggested to be a potential therapy at low dosage for multiple inflammatory conditions and cancers. Little is known about the immune-modulating effects of naltrexone, but an effect on the activity of toll-like receptor 4 (TLR4) has been reported. We analyzed the effects of naltrexone hydrochloride on IL-6 secretion by peripheral blood mononuclear cells (PBMC) in vitro following stimulation with ligands for TLR4 and for the intracellular receptors TLR7, TLR8, and TLR9. Naltrexone did not affect cell viability or induce apoptosis of PBMC. Intracellular staining demonstrated that naltrexone inhibited production of IL-6 and TNFα by monocyte and plasmacytoid dendritic cell subsets within the PBMC population following treatment with ligands for TLR7/8 and TLR9, respectively. No effect of cytokine production by PBMC following stimulation of TLR4 was observed. Additionally, naltrexone inhibited IL-6 production in isolated monocytes and B cells after TLR7/8 and TLR9 stimulation, respectively, but no effect on IL-6 production in isolated monocytes after TLR4 stimulation was observed. These findings indicate that naltrexone has the potential to modulate the secretion of inflammatory cytokines in response to intracellular TLR activity, supporting the hypothesis that it may have potential for use as an immunomodulator.
Highlights
Naltrexone hydrochloride is an opioid antagonist used commonly in the treatment of opioid and alcohol dependence [1, 2]
peripheral blood mononuclear cells (PBMC) were stimulated with toll-like receptor (TLR)-Ls for toll-like receptor 4 (TLR4) (LPS 1 ng/ml), TLR7/8 (R848 1μM), and TLR9 (CpG 1μM) in the presence or absence of naltrexone (1–200μM), and IL-6 production was determined by ELISA
Naltrexone had no effect on IL-6 production following TLR4 stimulation (Figure 1A); 200μM naltrexone inhibited IL-6 production following stimulation with ligands for TLR7/8 (Figure 1B, p < 0.05) and TLR9 (Figure 1C, p < 0.05)
Summary
Naltrexone hydrochloride is an opioid antagonist used commonly in the treatment of opioid and alcohol dependence [1, 2]. Naltrexone inhibits the mu and, to a lesser extent, the delta opioid receptors [3], preventing the euphoric effects of alcohol or opioid. It has been suggested that treatment with low-dose naltrexone (LDN) may be beneficial for a range of inflammatory conditions, including Crohn’s disease [4], multiple sclerosis [5], and fibromyalgia [6,7,8]. Naltrexone and the related opioid antagonist naloxone have been shown to inhibit the activity of a member of the toll-like receptor (TLR) family, TLR4, in an in vitro signaling assay and to reverse neuropathic pain in an animal model [15, 16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
