Opioids in Immunologic Processes

Bryant, Henry U.; Holaday, John W.

doi:10.1007/978-3-642-77540-6_15

Cited by 12 publications

(10 citation statements)

References 130 publications

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“…Altogether, pharmacological studies suggest that morphine immunosuppression is mediated by multiple mechanisms without providing any clue on the exact nature of receptor sites that mediate morphine action at the molecular level. In our study we have observed lymphoid organ atrophy as well as strong reduction of NK cytotoxicity in wild-type hybrid 129͞sv ϫ C57BL͞6 mice after chronic morphine administration, as described in other mouse strains (6). Most importantly, these two well-described immunosuppressive actions of morphine are absent in MORdeficient mice.…”

Section: Discussionsupporting

confidence: 82%

“…Indeed, data obtained from the administration of opioid antagonists in vivo have provided controversial results because the opioid antagonists naloxone and naltrexone have been shown to exert enhancing (26) inhibitory effects (20,22) or no effect (reviewed in ref. 6) on immune function. Furthermore, the lack of receptor subtype selectivity of those compounds does not allow to conclude on the specific involvement of -opioid receptor sites in the regulation immune function under physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Morphine reduces immunocompetence in vivo by molecular mechanisms that remain to be established. Morphine has been shown to influence the immune system in both naloxonesensitive and insensitive manners (6). Some effects, including lymphoid organs atrophy, could be reversed partially or totally by the opioid antagonists naloxone and naltrexone (20,27).…”

Section: Discussionmentioning

confidence: 99%

“…Another potential drawback is the inhibitory action of morphine on immune responses. More generally, the suppressive effect of opiates on immune responses has been demonstrated both in animal models and humans (5,6), and was shown to account for increased susceptibility to infections (6,7).…”

mentioning

confidence: 99%

“…In any instance, receptors that represent primary sites for opiate action have been poorly characterized. The demonstration of naloxonesensitive effects (6) has suggested an implication of the classically described , ␦, and opioid receptor sites (12). Naloxone-insensitive actions of opiates were also reported and the existence of nonclassical opioid receptors that would specifically bind the C-terminal portion of ␤-endorphin (13), or recognize alkaloids but not peptidic opioid ligands (14), has been proposed.…”

mentioning

confidence: 99%

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Abolition of morphine-immunosuppression in mice lacking the μ-opioid receptor gene

Gavériaux‐Ruff

Matthes

Peluso

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

148

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Opiates are potent analgesic and addictive compounds. They also act on immune responses, and morphine, the prototypic opiate, has been repeatedly described as an immunosuppressive drug. Pharmacological studies have suggested that the inhibitory action of opiates on immunity is mediated by multiple opioid receptor sites but molecular evidence has remained elusive. Recently, three genes encoding -(MOR), ␦-, and -opioid receptors have been cloned. To investigate whether the -opioid receptor is functionally implicated in morphine immunosuppression in vivo, we have examined immune responses of mice with a genetic disruption of the MOR gene. In the absence of drug, there was no difference between wild-type and mutant mice with regard to a large number of immunological endpoints, suggesting that the lack of MOR-encoded protein has little consequence on immune status. Chronic morphine administration induced lymphoid organ atrophy, diminished the ratio of CD4 ؉ CD8 ؉ cells in the thymus and strongly reduced natural killer activity in wild-type mice. None of these effects was observed in MOR-deficient mice after morphine treatment. This demonstrates that the MOR gene product represents a major molecular target for morphine action on the immune system. Because our previous studies of MOR-deficient mice have shown that this receptor protein is also responsible for morphine analgesia, reward, and physical dependence, the present results imply that MOR-targeted therapeutic drugs that are developed for the treatment of pain or opiate addiction may concomitantly inf luence immune responses.

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Section: Discussionsupporting

confidence: 82%