Hematopoietic effect of melatonin involvement of type 1 kappa-opioid receptor on bone marrow macrophages and interleukin-1

Melatonin has immune-enhancing properties and exerts colony-stimulating act ivity (CSA) via T-helper cell-derived opioids. Opioid agonists may mimic th e CSA of melatonin with an order of potency that suggests the presence of a type 1 kappa-opioid receptor (type 1 kappa OR [kappa 1-OR]). The kappa OR antagonist nor-binaltorphimine neutralized the in vitro effect of melatonin and inhibited regeneration of hematopoiesis in mice treated with carboplat in. The CSA of dynorphin A was abolished by incubation of adherent cells wi th antisense (AS) oligodeoxynucleotide to kappa OR or by addition of anti-i nterleukin (IL)-1 monoclonal antibody (mAb), which also neutralized the eff ect of melatonin. Bone marrow cells that express kappa ORs were identified to be macrophages. In conclusion, we describe the presence of kappa ORs in bone marrow macrophages and suggest a hematopoietic function for melatonin via endogenous kappa-opioid agonists and, possibly, IL-1.