Opioid immune system

It is well established that NF-kB signaling plays a critical role in inflammation and immunity. Understanding the mechanism of NF-kB involvement in opioid receptor activation and chemokine expression may provide a vital key to understanding this complex signaling network. However, the elucidation of molecular mechanisms following activation of the opioid receptor family could aid in the development of future therapeutics for immune system-related and inflammatory diseases, drug addiction and HIV infection. 

Opioid regulation of chemokine and chemokine receptor expression has several disease- related implications. Viral infection by HIV-1 can be enhanced with opioids that activate MOR while the opposite can be true for opioids that activate KOR. Increased levels of HIV-1 coreceptors, such as CCR5 and CXCR4, can promote viral binding and trafficking of HIV-1 virally infected cells. It is likely that this allows the viral disease to progress in the immune cells of the blood in addition to neurological reservoirs. Alterations of chemokine receptor expression will not only affect viral infection, but also alter immune system function. In certain diseases... 

Bidlack JM (2000) Detection and function of opioid receptors on cells from the immune system. 

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... 

Another site of action for opioids is through the regulatory actions of the central nervous system (CNS) on the immune system. Substantial evidence supports the existence of a complex, bidirectional link between the CNS and the immune system (e.g., [65]). Experimental evidence indicates that morphine s immunomodulatory effects involve central opioid receptors. An initial study by Shavit and colleagues [12] found that systemic administration of morphine, but not N-methylmorphine (a form of morphine which does not readily penetrate the blood-brain barrier), produces a naltrexone-reversible suppression of splenic natural killer cell activity in the rat. That same study showed that intracerebroventricular (icv) administration of morphine dose-dependently suppresses... 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, 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... 

Recently, Sedqi et al. [24] were able to clone a delta opioid receptor complementary DNA by expression of cDNA library from activated thymocytes in Cos 7 cells, whose amino acid sequence was similar to the neural counterpart. Interestingly, they also observed that transcripts for kappa and mu opioid receptors were not detected in thymocytes. Furthermore, Gave-riaux et al. [25] demonstrated transcripts for the delta opioid receptor in T-lymphocyte, B-lymphocyte, and monocyte cell lines, as well as in murine splenocytes. However, they observed that the kappa opioid receptor transcript was only found in B-cell lines. These studies may suggest a selective expression of the delta opioid receptor in specific cells and tissues of the immune system and suggests specialized functions in different anatomical regions. 

The direct effects opioid and opioidlike peptides exhibit on cells of the immune system is both varied and, in some instances, contradictory, depending on which receptor subtype is being studied. Mu and kappa receptors generally affect immunofunction in a suppressive manner, where delta receptors tend to express immunostimulation [82-85]. However, selected delta antagonists have shown to elicit suppressive effects on B-cell proliferation, NK cell activity, and T-helper cell cytokine production [86]. The alteration of leukocyte function via opioid receptors will be discussed highlighting specific cell subtype immunomodulation. Endorphin shows a inhibitory effect on splenocyte proliferation through central and peripheral autocrine/paracrine pathways [87]. 

Klebsiella pneumoniae infection in mice after intravenous treatment (Meisel and Schlimme, 1996). The mechanism by which milk protein derived peptides exert their immunomodulatory effects is not yet defined. However, opioid peptides may affect the immunoreactivity of lymphocytes via the opiate receptor. There is a remarkable relationship between the immune system and opioid peptides, because opioid p, receptors for endorphins are present on T lymphocytes and human phagocytic leukocytes (Meisel, 1998). 

Opioid receptors are present in human T-cell lymphocytes (Wybran et al., 1979), which may provide a link between the central nervous system and the immune system. There is a considerable body of literature, which demonstrates a modulatory function of the immune system by opioids. Opioids alter the biochemical and proliferative properties of various cellular components of the immune system (Webster, 1998). (3-Casomorphins affect the human mucosal immune system, possibly via the opiate receptor, since the opiate receptor antagonist, naloxone, reverses the activity (Elitsur et al., 1991). P-Casomorphins and a-casein exorphins inhibit the cell proliferation of human prostate cell lines by a mechanism partly involving opioid receptors (Kampa et al., 1997). 

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