Opioid‐Induced Alterations of TLR4 Protein Expression in a Human Microglial Cell Line

Abstract

Opioids are recognized to modulate immune function; however, the exact mechanisms for altered immune responses continue to be elusive. The current research investigates the role of toll-like receptor 4 (TLR4) protein expression in response to opioids in central nervous system (CNS) immunomodulation. Human CHME-5 microglia were treated with morphine, methadone, oxycodone, or buprenorphrine at the concentrations of 3-33 µM either alone or with a single dose of 100 ng/mL of lipopolysaccharide (LPS). Morphine at 10 µM upregulated TLR4 protein expression in the presence of LPS. The most pronounced effect occurred with methadone, which at 3 µM and 10 µM also upregulated TLR4 protein expression; however, methadone with LPS at all concentrations had the opposite effect (p<0.05). 33 µM oxycodone + LPS, 10 µM buprenorphrine + LPS, and 33 µM buprenorphrine alone also downregulated TLR4 protein expression (p<0.05). As opioid use increases the likelihood for opportunistic infection, these changes in TLR4 expression may be a contributing factor in the development and treatment of CNS infection and neurodegeneration. This work was supported by OCAST Oklahoma Health Research Program HR 10-31 (CWS) and NIH grant NS 062664 (RLD).