Effect of melatonin and β-endorphin interaction in splenocyte proliferation

Abstract

Abstract: BACKGROUND: Opioids in the circulation interact with lymphocytes, suggesting a possible link between the neuroendocrine system and the immune system. AIMS AND OBJECTIVES: We examined the in vitro pattern of immunomodulatory effects (T-cell proliferation and pro-inflammatory cytokine production) by β-endorphin and melatonin, along with or without their respective receptor antagonists (naloxone and luzindole), on the splenocytes of boar golden hamsters. MATERIALS AND METHODS: We performed the in vitro proliferation assay in terms of blastogenic response or percent stimulation ratio of the splenocyte culture. Cytokine determination for interleukin-6 (IL-6), IL-2, and interferon-γ (IFN-γ), immunocytochemical localization, and Western blot analysis of melatonin receptor (MT1R) and opioid receptor (μOR) were also analyzed from splenocyte culture. RESULTS: Results suggested that splenocyte populations were targeted for the opioids that enhanced T-cell proliferation via the nonopiate receptor signaling pathway. Further, in vitro melatonin supplementation in splenocytes might be acting as an immunostimulator by increasing the level of cytokines (IL-6, IL-2, and IFN-γ) and its own melatonin MT1R membrane protein synthesis and downregulating μ-opioid receptor (μOR) expression, suggesting melatonin-induced-nociceptive or anti-stress effects. CONCLUSION: Our results concluded that the mechanism of the immunoproliferative response of splenocytes by the treatment of β-endorphin and melatonin significantly induced the level of pro-inflammatory cytokines through the enhanced synthesis of melatonin MT1R and reduced opioid µΟR proteins. Melatonin also induced endorphin-like opioid peptide synthesis, which could mediate the fine-tuning of splenocyte proliferative responses along with analgesic effects. Thus, melatonin and β-endorphin together are fine-tuning the splenocyte proliferative responses.