Opioids modulate interleukin-1 production and secretion by bone-marrow macrophages

In the present study, we have assessed the effect of opioids (endorphins, enkephalins and neoendorphins) on production of IL-1 activity by bone-marrow-derived macrophages. None of the neuropeptides induced IL-1 production by itself. However, some of the opioids potentiated IL-1 production and release in macrophages concomitantly stimulated by lipopolysaccharide (LPS) or silica. LPS induced predominantly intracellular IL-1 activity, whereas most of the silica-induced IL-1 was released extracellularly. β-Endorphin, leucin-enkephalin (leu-enkephalin) and β-neoendorphin all potentiated both intracellular and extracellular release of IL 1 induced by either LPS or silica. In contrast, α-endorphin, methionine-enkephalin (metenkephalin) and α-neoendorphin did not influence IL-1 production or release. The potentiating effects of β-endorphin on LPS-induced IL-1 production/secretion were inhibited by naloxone, pointing to an involvement of opioid receptors.