Opioids immunosuppression

Three endogenous opioids have been identified enkephalins, dynorphins and beta-endorphins. These opioid peptides selectively bind to the seven transmembrane GPCRs delta (8), kappa (k), and mu (p). Although dynorphin binds predominately to the k receptor, P-endorphines and enkephalins bind to p and 8 opioid receptors. It is important to note that the analgesia induced by opioids is mediated predominately throngh the p opioid receptor. In vitro studies have shown a decrease in the immnne function and proliferation following p-endorphin administration in rodents (Ray and Cohn 1999) and that the immunosuppressive effects by P-endorphins are steroid-independent (Berkenbosch et al. 1984 Nelson et al. 2000). 

Vallejo R, de Leon-Casasola O, Benyamin R (2004) Opioid therapy and immunosuppression a review. Am J Ther 11 354-365... 

Arakawa K, Akami T, Okamoto M, Akioka K, Nakai I, Oka T, Nagase H. Immunosuppression by delta opioid receptor antagonist. Transplant Proc 1993 25 738-740. 

Opioids induce the release of histamine, which leads to the itching sensation associated with use and abuse of opioids. Bronchiolar constriction is possible. Opioids are also immunosuppressive, having effects on the T-helper and T-suppressor cells. 

The activity of a prototypical delta antagonist was also tested in vivo. The immunosuppressive effect of NTI was maintained in delta receptor knockout mice, as well as in mice lacking all three opioid receptors [68], opening the search for a novel molecular target for this widely used delta opioid compound. 

In conclusion, the in vivo activity of available delta opioids is complex. DPDPE, or even Delt, administered ICV seems to recruit mu receptors and, from all the data, it appears that delta agonists often have mixed mu/ delta activities. More selective delta agonists need to be produced to explore delta receptor pharmacology. The examination of nonanalgesic activities of delta ligands in opioid receptor knockout mice has been very informative while the convulsive effect of SNC 80 seems indeed delta receptor mediated, the addictive activity of Delt most probably results from mu receptor activation and the immunosuppressive action of NTI is mediated by a nonopioid mechanism. 

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. 

Be aware that OTC medications, nutritional supplements and herbal medications can interact in known and unknown ways to cause an inhibition/induction of metabolizing enzymes and transport mechanisms. The constituents can cause additive/antagonist effects and adverse life-threatening interactions, particularly in people on medications discussed in the main sections (e.g. MAOI antidepressants, opioids, corticosteroids, immunosuppressants, anticoagulants). 

Keywords Cannabinoids Cheniokines Cocaine Cytokines Immunosuppression Morphine Opioids T-helper 1/T-helper 2 (Thl/Th2) A9-tetrahydrocannabinol (A -THC) Tolerance Withdrav al... 

Eisenstein TK, Meissler Jr JJ, Rogers TJ, Geller EB, Adler MW (1995) Mouse sdaiii differences in immunosuppression by opioids in vitfo. J Phai macol Exp Tlier 275 1484—1489. 

Guan L, Townsend R, Eisenstein TK, Adler MW, Rogers TJ (1994) Both T cells and macrophages are targets of K-opioid-induced immunosuppression. Brain Behav hnmun 8 229—240. 

Keywords Acetylcholine Autonomic nervous system Cyclosporine Epinephrine General anesthetics Immunostimu-lating agents Immunosuppressive agents Mycophenolate mofetil Opioid drugs Sedative-hypnotic agents... 

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