ministration, and the immune response under study. Using animal models, researchers have discovered that acute administration of the prototypical μ opioid receptor agonist morphine reduces natural killer cell activity, mitogen-induced T- and B-cell proliferation, and interleukin-2 and interferon production (Lysle et al., 1993), as well as antibody production (Lockwood et al., 1994) in activated splenocyte cultures. Morphine has also been shown to inhibit Fc-mediated phagocytosis through receptor binding (Tomassini et al., 2003) and increase murine macrophage and human monocyte apoptosis (Kapasi et al., 2004). Not only have opioid receptors been shown to be immunosuppressive, but activity at μ opioid receptors also has immunoenhancing effects. Morphine has been shown to increase macrophage-derived nitric oxide production (Fecho et al., 1994), protect against murine HSV I infection (Alonzo & Carr, 1999), and enhance contact hypersensitivity (CHS) (Nelson et al., 1999). Thus, the immunoregulatory roles of μ opioid receptors and their associated ligands on the immune system are complex.
             In addition to opioid receptor involvement in the immunomodulatory effects of opioids, κ and δ receptor activity may also contribute to alterations of immune function. Treatment with the κ receptor agonists MR 2034 and U50,488 suppressed the plaque-forming cell response in rats (Radulovic, et al., 1994) and peritoneal macrophage phagocytosis in mice (Szabo, et al., 1993), respectively. Intracerebroventricular (ICV) administration of the δ opioid receptor agonist SNC 80 has been shown to increase splenic lymphocyte proliferation in rats compared to controls (Nowak, et al., 1998), and intravenous (IV) administration increased macrophage-derived nitric oxide and tumor necrosis factor-α (TNF-α) production in rats (Gomez-Flores et al., 2001). Other studies have demonstrated immunosuppressive effects of selective δ agonists, such as inhibiting elicit...