Effects of endogenous and synthetic opioid peptides on neutrophil function in vitro

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Opioid peptides released from immunocytes during inflammation and stress in critically ill patients are associated with an altered immune response. Moreover, concentrations of opioid peptides are increased in peripheral blood and at the sites of inflammatory reactions.


Using flow cytometric assay of whole human blood, we investigated direct effects of endogenous and synthetic opioid peptides on surface expression of complement receptors CD35 and CD11b/CD18 and Fcã receptor III CD16, and superoxide anion generation of neutrophils.


The endogenous opioid peptides β-endorphin1–31 and met-enkephalin, representing the N-terminal fragment of β-endorphin1–31, and the synthetic δ opioid receptor agonists D-Ala2-D-Leu5-enkephalin and D-Pen2-enkephalin produced concentration-dependent stimulation of neutrophil activity. Incubation with met-enkephalin 10–7 M or β-endorphin1–31 10–7 M led to an increase in receptor expression of up to 10% (met-enkephalin) and 15% (β-endorphin1–31). After incubation with D-Ala2-D-Leu5-enkephalin or D-Pen2/5-enkephalin, receptor expression was increased by up to 30%. This correlated with concentration-dependent stimulation of the production of reactive oxygen intermediates, as shown by an increase of up to 40% in oxidative burst activity. All effects were abolished after preincubation with naloxone or with the selective δ opioid antagonist naltrindole, whereas the selective µ receptor antagonist d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 showed only partial inhibitory effects.


Our data suggest a δ opioid receptor-mediated stimulatory effect on neutrophil function. β-Endorphin27–31, the C-terminal fragment of β-endorphin1–31, did not alter neutrophil function, indicating that β-endorphin1–31 mediates its effect on neutrophils via the N-terminal fragment. This study may contribute to a better understanding of neuroimmune interaction.

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