Endomorphin-1 alters interleukin-8 secretion in Caco-2 cells via a receptor mediated process

Administration of opioids that bind to the classical mu opioid receptor has been shown to lead to unintended alterations in immune function. Traditionally, altered immune function has been investigated with circulating immune cells. Effects of mu agonists on intestinal epithelial immune function have not been described. Since the oral route of administration is frequently employed with opiates, we determined if the mu receptor specific agonist endomorphin-1 altered interleukin-8 (IL-8) production by Caco-2 cells. Using RT-PCR and immunocytochemistry, Caco-2 cells were found to constitutively express (mu) mu opioid receptors. Activation of the mu receptor by endomorphin-1 (1 and 10 microM) resulted in significant increases in IL-8 when Caco-2 cells were stimulated with IL-1beta. Increased IL-8 secretion due to endomorphin-1 could be blocked by pre-incubating cells with the mu receptor antagonist, beta-funaltrexamine. These results indicate that the intestinal epithelial IL-8 response can be altered by a muopioid receptor mediated mechanism.