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

Abstract

Administration of opioids that bind to the classical μ 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 μ 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 μ 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) μ opioid receptors. Activation of the μ receptor by endomorphin-1 (1 and 10 μM) resulted in significant increases in IL-8 when Caco-2 cells were stimulated with IL-1β. Increased IL-8 secretion due to endomorphin-1 could be blocked by pre-incubating cells with the μ receptor antagonist, β-funaltrexamine. These results indicate that the intestinal epithelial IL-8 response can be altered by a μ opioid receptor mediated mechanism.