Equianalgesic Doses of Subcutaneous but Not Intrathecal Morphine Alter Phenotypic Expression of Cell Surface Markers and Mitogen-induced Proliferation in Rat Lymphocytes

Hamra, Jena; Yaksh, Tony L.

doi:10.1097/00000542-199608000-00018

Cited by 40 publications

(17 citation statements)

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“…The pharmacokinetics, pharmacology, adverse effects and clinical use guidelines of the drug have been reviewed in detail by Duthie 4 and Shipton. 5 Since it is well established that opioids modulate immune responses including an inhibitory effect on phagocytosis, [6][7][8][9] the aim of the present study was to compare the in vitro effect of tramadol with that of morphine on the engulfing capacity of peripheral blood phagocytic cells from healthy volunteers.…”

Section: Méthodementioning

confidence: 99%

Tramadol does not impair the phagocytic capacity of human peripheral blood cells

Beilin

Grinevich

Yardeni

et al. 2005

Can J Anesth/J Can Anesth

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Purpose:The inhibitory effect of opioids on phagocytic cell capacity is well established. However, the effect of synthetic analgesics on this aspect of cell function is controversial. It was the aim of the study to compare the in vitro effect of tramadol with that of morphine on the engulfing ability of peripheral blood phagocytic cells from healthy volunteers. Methods:Peripheral blood polymorphonuclear cells and monocytes from healthy volunteers were incubated with 5, 10 and 20 µg·mL -1 tramadol, or with 20, 40 and 80 ηg·mL -1 morphine. To each tube, 0.05 mL of 5% suspension of latex beads 0.8 µm in diameter was added. After incubation for 60 min the percentage of cells engulfing latex particles and the phagocytic index (number of particles phagocytized by each individual cell) were detected. Results:Tramadol affected neither the percentage of cells phagocyting latex particles, nor the phagocytic index of both polymorphonuclear cells and monocytes. On the other hand, incubation with 20, 40 and 80 ηg·mL -1 morphine caused 11%, 14% and 24% decrease in phagocytosis (P < 0.01 -P < 0.001). The percentage of monocytes phagocyting latex particles was lower by 16%, 19% and 12% at the three doses tested (P < 0.01 -P < 0.001). The three doses of morphine caused a dose dependent decrease in the monocyte phagocyting index by 20%, 29% and 35.5% respectively (P < 0.05). The polymorphonuclear phagocyting index was not significantly lower following incubation with the drug (P = 0.053). Conclusion:The lack of noxious effect of tramadol on the engulfing capacity of phagocytic cells suggests additional benefit to the relatively safe profile of the drug. 20 %, 29 % et 35,5 % (P < 0,05). L'indice phagocytaire des polynucléaires n'était pas significativement plus bas à la suite de l'incubation avec le médicament (P = 0,053 Objectif : L'effet inhibiteur des opioïdes sur la capacité des cellules phagocytaires est bien établi. Mais l'effet des analgésiques synthé-tiques est controversé. Nous voulions comparer l'effet in vitro du tramadol et de la morphine sur la capacité d'englobage que possèdent les cellules sanguines phagocytaires périphériques prélevées chez des volontaires sains. Méthode

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Section: Méthodementioning

confidence: 99%

Tramadol does not impair the phagocytic capacity of human peripheral blood cells

Beilin

Grinevich

Yardeni

et al. 2005

Can J Anesth/J Can Anesth

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“…Es muss jedoch zwischen 2 grundsätzlichen Mechanismen der Opioid-induzierten Immunmodulation unterschieden werden: Während bei Invitro-Experimenten zahlreiche direkte Effekte auf Immunzellen beobachtet wurden [54,101], postulieren zahlreiche In-vivo-Studien nicht nur einen direkten [36,37], sondern auch einen indirekten Einfluss von Opioiden auf die Immunfunktion über das zentrale Nervensystem [60,68]. Über zentrale Opioidrezeptoren werden insbesondere lymphozytäre Funktionen, wie die NK-Zell-Aktivität und die Lymphozytenproliferation, aber auch die zelluläre und humorale Immunantwort beeinflusst.…”

Section: Opioid-induzierte Immunsuppressionunclassified

“…Im Gegensatz hierzu wird die Mitogen-stimulierte Lymphozytenproliferation in In-vivo-Experimenten an der Ratte sowohl durch intrathekales Morphin als auch durch intrathekales NMethylmorphin inhibiert [37]. Hinweise darauf, dass die für die Immunmodulation entscheidenden Rezeptoren supraspinal lokalisiert sein müssen, liefert eine In-vivo-Untersuchung an Ratten, bei der die subkutane Applikation einer analgetisch wirksamen Dosis Morphin das Expressionsmuster lymphozytärer Oberflächenmoleküle veränderte und die Lymphozytenproliferation hemmte [36]. Dagegen blieb die intrathekale Gabe einer äquianalgetischen Morphindosis ohne immunmodulierende Effekte [36].…”

Section: Opioid-induzierte Immunsuppressionunclassified

“…Hinweise darauf, dass die für die Immunmodulation entscheidenden Rezeptoren supraspinal lokalisiert sein müssen, liefert eine In-vivo-Untersuchung an Ratten, bei der die subkutane Applikation einer analgetisch wirksamen Dosis Morphin das Expressionsmuster lymphozytärer Oberflächenmoleküle veränderte und die Lymphozytenproliferation hemmte [36]. Dagegen blieb die intrathekale Gabe einer äquianalgetischen Morphindosis ohne immunmodulierende Effekte [36]. Einen weiteren wichtigen zentralen Wirkmechanismus von Morphin stellt die Modulation der Stressreaktion über die hypothalamo-hypophysär-adrenale Achse dar [60].…”

Section: Opioid-induzierte Immunsuppressionunclassified

“…Diese Verände-rungen konnten 24 h nach Implantation des Morphin-Pellets mit Hilfe von monoklonalen Antikörpern durchflusszytometrisch bestimmt werden und waren über 3 Tage nachweisbar. Bislang ist jedoch völlig ungeklärt, ob und inwieweit eine Suppression der Lymphozytenproliferation um 20-30% [36] oder eine zwar signifikante, aber prozentual geringe Reduktion von Oberflächenmarkern durch Morphin [100] klinische Relevanz besitzt.…”

Section: Veränderungen Der Leukozytenfunktion Durch Morphinunclassified

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Opioide und Immunsuppression

Welters¹

2003

Der Anaesthesist

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First observations that opioids may have disadvantageous effects on the immune response have been made more than 100 years ago. Today the immunosuppressive effect of morphine is well established.Drug-induced immunomodulation is of growing importance in modern anesthetic concepts. The reduced stress response observed after morphine application contributes to this effect as well as direct impairment of immune effector cells such as bactericidal activity, intracellular killing,proliferative response or cytokine synthesis. Opioid-induced immunomodulation is mediated by opioid receptors found on immunocytes and in the central nervous system.A negative feedback mechanism via the hypothalamo-pituitary-adrenal axis may potentiate the direct inhibitory effect of morphine on the immune response.A final statement regarding the clinical relevance of opioid-induced immunosuppression cannot be made at this point, since the existing clinical data are preliminary and inconclusive.Therefore, further clinical studies are mandatory to elucidate the influence of opioid treatment on immune regulation in different clinical settings in anesthesia, critical care, pain therapy and emergency medicine. Further investigations may help to not only provide sufficient analgesia by application of opioids, but also to assess advantages and disadvantages on immune function.

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Phenotypic Analysis of Splenocyte Subsets Following Acute Morphine Treatment in the Rat

Fecho

Lysle

1999

Cellular Immunology

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Equianalgesic Doses of Subcutaneous but Not Intrathecal Morphine Alter Phenotypic Expression of Cell Surface Markers and Mitogen-induced Proliferation in Rat Lymphocytes

Cited by 40 publications

References 46 publications

Tramadol does not impair the phagocytic capacity of human peripheral blood cells

Tramadol does not impair the phagocytic capacity of human peripheral blood cells

Opioide und Immunsuppression

Phenotypic Analysis of Splenocyte Subsets Following Acute Morphine Treatment in the Rat

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