Translational potential of naloxone and naltrexone as TLR4 antagonists

Abstract

In the recent TiPS review by Watkins et al. [1], as well as subsequent reports [2] and reviews [3], opiate antagonists (naloxone and naltrexone) are claimed to inhibit Toll-like receptor 4 (TLR4) signaling in a nonstereoselective fashion. These claims are based on the foundational in vitro finding that both enantiomers effect a ‘…dose dependent blockade of TLR4 by LPS [lipopolysaccharide], a classical TLR4 agonist, as indicated by suppression of LPS-induced reporter protein in a TLR4 expressing cell line’ [1].