MODULATORY EFFECTS OF [MET(5)]-ENKEPHALIN ON INTERLEUKIN-1-BETA SECRETION FROM MICROGLIA IN MIXED BRAIN-CELL CULTURES

In the present study, functional interactions between [Met(5)]-enkepha lin (ME), naloxone and lipopolysaccharide (LPS) on interleukin-1 beta (IL-1 beta) immunostaining and secretion have been assessed in mixed b rain cell cultures from embryonic day 17 mice. Adding ME alone or toge ther with LPS to the culture increased the release of IL-1 beta after 48 h in a concentration-dependent fashion. In situ hybridization studi es showed that LPS, but not ME, increased the abundance of IL-1 beta m RNA. The enhanced release of IL-1 beta caused by ME or LPS was partial ly blocked by naloxone. LPS induced concentration-dependent morphologi cal changes in microglia in mixed brain cell cultures, identified by a monoclonal antibody F4/80 which is specific for macrophages/microglia . Despite increasing IL-1 beta release into the media, ME (10(-8) M) d id not induce morphological changes in microglia. Naloxone alone also had no effect on glial morphology; however, the LPS-induced morphologi cal changes were blocked by naloxone. Our data indicate that both exog enous and endogenous opioids regulate IL-1 beta production by microgli al cells in the mixed brain cell cultures.