Opioids immune function

Since initial studies identified opioid receptors on T-lymphocytes (Wybran et al. 1979), the effects of opioids on immune function have been extensively studied. Details of these studies have been exhaustively reviewed (Madden et al. 1991 Adler et al. 1993 Peterson et al. 1998 Donahoe and Vlahov 1998 Roy et al. 2006), and will only be briefly mentioned here. In general, opioids suppress immune function. Peripheral leukocytes, including lymphocytes and peripheral blood mononuclear cells (PBMCs) can express the four major opioid receptor types, MOP, DOP, KOP,... 

The endogenous opioids are another family of peptides involved in different physiological processes including pain regulation, respiratory control, stress responses, appetite, thermoregulation, and humoral and cellular immune function (Bodnar RJ., 2008). Opioids act through their receptors, which are also members of the GPCR family, and are expressed in the central and peripheral nervous system as well as on cells of the immune system (Henriksen and Willoch 2008 Hauser... 

Lysle, D.T., Luecken, L.J., and Maslonek, K.A., Modulation of immune function by a conditioned aversive stimulus Evidence for the involvement of endogenous opioids, Brain, Behav. Immun., 6, 179, 1992. 

In addition to their use as pharmacological tools, selective 8 opioid antagonists may have clinical potential in the treatment of a variety of disorders where endogenous opioids play a modulatory role, e.g. disorders of food intake, shock, constipation, mental disorders, CNS injury, alcoholism, drug addiction and immune function (Spetea et al., 2001). It is also worth mentioning that 8 antagonists have been shown to possess an antitussive effects in rodents, thus indicating another possible clinical application for these compounds (Kamei et al., 1994). 

The opioids may modulate the actions of the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. Natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could mediate a significant component of the changes observed in peripheral immune function. In general, these effects are mediated by the sympathetic nervous system in the case of acute administration and by the hypothalamic-pituitary-adrenal system in the case of prolonged administration of opioids. 

Novel opioid compounds have been synthesized that have analgesic capacity, but lack immunosuppressive effects or even potentiates immune function [60,123-126]. In this respect, Nowak et al. [123] recently reported that the delta opioid agonist SNC 80 did not alter NK cell, lymphocyte, and macrophage functions following ICV administration [123]. Furthermore, IV administration of SNC 80 was associated with ex vivo immunopotentiation, following an activating challenge. 

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