β-Endorphin modulation of IL-1-induced IL-2 production

Abstract

We have studied the effects of natural opioids on interleukin-1 (IL-1) -induced interleukin 2 (IL-2) production by the lymphoid cell line EL-4. β-Endorphin (β-end) significantly enhanced IL-2 production by IL-1-stimulated EL-4-cells. Similar results were obtained using the LBRM33-1A5 cell line. β-End induced significant enhancement (35–100%) of IL-1-induced IL-2 production at all concentrations of IL-1 tested (2-0.25 U/ml) and the effects were seen with both IL-1α and IL-1β. The dose response of β-end augmentation of IL-1-induced IL-2 production was bimodal, with peak activities seen at high (10−8–10−10M) and low (10−16M) β-end concentrations. The specificity of β-end effect was studied using the opioid antagonist naloxone. Naloxone completely abolished the enhancing effects of β-end, indicating that the effects might be mediated through binding to opioid receptors. In addition, other opioid peptides, including γ-endorphin and enkephalins, elicited similar effects. Northern blotting analysis revealed higher levels of IL-2 mRNA in β-end-treated IL-1-induced EL-4 cells than in IL-1-induced control cells. Thus, β-end might enhance IL-2 production by either augmenting the transcription rate or increasing IL-2 mRNA stability. These results suggest that β-end might play an important role in the regulation of lymphokine production in the periphery in addition to its known interactions with IL-1 in the central nervous system.