Beta-endorphin modulation of IL-1-induced IL-2 production

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. beta-Endorphin (beta-end) significantly enhanced IL-2 production by IL-1-stimulated EL-4 cells. Similar results were obtained using the LBRM33-1A5 cell line. beta-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-1 alpha and IL-1 beta. The dose response of beta-end augmentation of IL-1-induced IL-2 production was bimodal, with peak activities seen at high (10(-8)-10(-10) M) and low (10(-16) M) beta-end concentrations. The specificity of beta-end effect was studied using the opioid antagonist naloxone. Naloxone completely abolished the enhancing effects of beta-end, indicating that the effects might be mediated through binding to opioid receptors. In addition, other opioid peptides, including gamma-endorphin and enkephalins, elicited similar effects. Northern blotting analysis revealed higher levels of IL-2 mRNA in beta-end-treated IL-1-induced EL-4 cells than in IL-1-induced control cells. Thus, beta-end might enhance IL-2 production by either augmenting the transcription rate or increasing IL-2 mRNA stability. These results suggest that beta-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.