Hematopoietic effect of melatonin involvement of type 1 K‐opioid receptor on bone marrow macrophages and interleukin‐1

Abstract

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