Dynorphin and related subfragments augment splenic effector cell lytic function against YAC-1 tumor cells in vitro

Regulation of the immune system by the neuroendocrine system is a relatively new concept. We have investigated the influence of the opioid peptide dynorphin (DYN) and its subfragments on murine splenic natural killer (NK) cell cytotoxicity against YAC-1 cells in vitro. Addition of DYN or a/B interferon (IFN) significantly augmented NK lytic function in a 4 hour chromium release assay. Dynorphin added to effector cells previously incubated with a/B IFN showed an augmentation over a/B IFN priming alone. Dynorphin exerted its effects on NK cytotoxicity over a range of 10^-8M to 10¹⁰M, with 10^-9M having the optimal augmentation effect. Leucine-enkephalin and other DYN subfragments exerted similar patterns of augmentation. The opioid peptide-induced augmentation was blocked by the general opiate antagonist naloxone. Verapamil, a calcium channel blocker, also suppressed the effect of DYN and its subfragments on NK cells, indicating calcium dependence in augmentation. Thus, it appears that the neuroendocrine opioid peptide DYN and its subfragments act as regulatory molecules to augment murine NK cell lytic functions. This effect is mediated by functional opiate receptors on the NK cell surface, which can be blocked by naloxone. This study provides further evidence for the concept of a neuro-immuno regulatory axis in tumor surveillance models.