Bidirectional modulation of mouse natural killer cell and macrophage cytotoxic activities by enkephalins

Stimulation of a cellular immune function as measured by splenic natural killer (NK) cell activity has been described following systemic treatment with enkephalins. In this study, we evaluated the effects of the central administration of enkephalins on the splenic NK cell activity and macrophage cytotoxicity. Intracerebroventricular injection of leucine-enkephalin (LE) or methionine-enkephalin (ME) induced bidirectional modulation of NK cell and macrophage cytotoxic activities (suppression followed by enhancement). Administration of ME or LE at doses of 100 or 10 micrograms/mouse caused inhibition of NK cell and macrophage activity 2 h after injection. Enhancement of NK cells activity was observed at 96 h and macrophages cytotoxicity at 24 h after icv injection with both enkephalins. Pretreatment with naloxone (20 micrograms/mouse) inhibited the enkephalins-induced augmentation of NK cell and macrophage cytotoxic activity. These findings demonstrate that central actions of enkephalins produce changes in cytotoxicity of NK cells and macrophages.