ABSTRACT
I. INTRODUCTION For more than two decades, the direct immunomodulatory effects of opiate alkyloids and opioid peptides have been recognized. For example, both -endorphin and opioid peptide agonists selective for the delta subtype of opioid receptor (DOR) are known to modulate mitogen and T-cell receptor (TCR)–induced thymic and splenic T-cell proliferation and cytokine production [1-3]. Thus, selective DOR agonists, such as [D-Ala2-D-Leu5]-enkephalin (DADLE) and deltorphin, have been shown to attenuate the anti-CD3-ε-induced proliferation of highly purified murine splenic CD4 and CD8 T cells [2]. In similar experiments, higher concentrations (108-106 M) of DADLE and deltorphin partially suppressed interleukin (IL)-2 production. Moreover, -endorphin has been shown to amplify concanavalin-stimulated calcium mobilization by splenic T cells [4]. Although these studies provide pharmacological evidence for the presence of DORs on T cells, understanding the mechanism(s) underlying these and other functional effects has been hampered by the lack of direct evidence for the expression of DORs by immune cells. Recent studies have resolved this dilemma by demonstrating the expression of opioid receptor mRNAs and receptor proteins on lymphocytes and other cells involved in host defense and immunity.
