Inhibitory effect of morphine on granulocyte stimulation by tumor necrosis factor and substance P

Stefano, George B.; Kushnerik, Vadim; Rodriquez, Madeline; Bilfinger, Thomas V.

doi:10.1016/0192-0561(94)90008-6

Cited by 26 publications

(10 citation statements)

References 14 publications

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“…At higher concentrations, however, fentanyl and morphine reduced the hyperactivation of granulocytes and monocytes exposed to the stimulatory effect of plasma obtained from CPB patients. This effect is probably mediated by opioid receptors on monocytes and granulocytes (20,21).…”

Section: Discussionmentioning

confidence: 99%

Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute‐phase protein responses in patients undergoing cardiac surgery

Christensen

Tønnesen

Sørensen

et al. 1998

Acta Anaesthesiol Scand

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Section: Discussionmentioning

confidence: 99%

Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute‐phase protein responses in patients undergoing cardiac surgery

Christensen

Tønnesen

Sørensen

et al. 1998

Acta Anaesthesiol Scand

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“…In vitro studies have shown that opioids, at higher concentrations, reduced hyperactivation of granulocytes and monocytes exposed to the stimulatory effects of plasma obtained from CPB patients. 8,9 Therefore, the high-dose fentanyl in cardiac surgery might attenuate the surgical stress response better than inhalation anesthetics. This may well explain the suppressed G-CSF response in cardiac surgery.…”

Section: Discussionmentioning

confidence: 99%

Neutrophilia and granulocyte colony-stimulating factor levels after cardiopulmonary bypass

Iwasaka

Kitano

Miyakawa

et al. 2001

Can J Anesth/J Can Anesth

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Purpose: The precise mechanism of neutrophilia after cardiac surgery is unknown. Granulocyte colony stimulating factor (G-CSF) can increase the number of leukocytes. The purpose of this study was to evaluate the relationship between serum G-CSF levels and peripheral blood leukocyte counts after cardiac surgery. Methods:We prospectively studied 10 patients undergoing cardiac surgery (coronary artery bypass grafting) using cardiopulmonary bypass (CPB). Plasma G-CSF levels and neutrophil count were measured before induction of anaesthesia, at the end of surgery, and on the first postoperative day. These changes were compared with those in patients undergoing non-cardiac major surgery (control group).Results: At the end of surgery, G-CSF levels increased (P < 0.01) in both groups, but were higher in the control than in the cardiac group (3,250 ± 690 vs 194 ± 29.5 pg·ml -1 , respectively, mean ± SEM, P < 0.01). On the first postoperative day, G-CSF levels were still high in both groups, and were still higher in the control (710 ± 179 vs 122 ± 19.9, respectively, P < 0.01). However, neutrophilia was greater in the cardiac group than in the control. G-CSF response correlated positively with neutrophilia in the control group (r=0.656, P < 0.05) but not in the cardiac group. Conclusions:Our results indicate that changes in leukocyte count following cardiac surgery are unique to patients undergoing CPB. G-CSF plays an important role as the mediator of neutrophilia after non-cardiac surgery, but not after cardiac surgery with CPB.Objectif : Le mécanisme précis de la polynucléose neutrophile qui survient après une intervention en cardiochirurgie est inconnu. Le facteur stimulant la formation de colonies de granulocytes (FSC-G) peut augmenter le nombre de leucocytes. L'objectif de la présente étude était d'évaluer la relation entre les niveaux sériques de FSC-G et la numération leucocytaire du sang périphérique à la suite d'une intervention cardiaque.Méthode : Nous avons mené une étude prospective auprès de 10 patients qui ont subi un pontage aorto-coronarien sous circulation extracorporelle (CEC). Les niveaux plasmatiques de FSC-G et la numération des neutrophiles ont été mesurés avant l'induction de l'anesthésie, à la fin de l'opération et au premier jour postopératoire. Les changements ont été comparés avec ceux qu'on a observés chez des patients qui ont subi une intervention importante, non cardiaque (groupe témoin).Résultats : À la fin de l'opération, les niveaux de FSC-G ont augmenté (P < 0,01) dans les deux groupes, mais ont été plus élevés dans le groupe témoin que dans le groupe de cardiochirurgie (3,250 ± 690 vs 194 ± 29,5 pg·ml -1 , respectivement, moyenne ± écart type, P < 0,01). Au premier jour postopératoire, les niveaux de FSC-G étaient encore élevés dans les deux groupes et toujours plus hauts chez les témoins (710 ± 179 vs 122 ± 19,9, respectivement, P < 0,01). Toutefois, la polynucléose neutrophile était plus marquée dans le groupe de cardiochirurgie que dans le groupe témoin. La réponse du FSC-G était en...

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“…Data are expressed as percent maximal relaxation in response to 1 M morphine. Opiate receptor specificity was evaluated by measurement of vascular relaxation in response to treatment with 1 M morphine rings pretreated for 10 min with 5 M naloxone or, for 3 ,Gly(ol) 5 ]enkephalin (DAGO). Rings of thoracic aorta (3 mm) were placed in PSS, and NO release in response to 1 M morphine was evaluated by use of a computer-interfaced NO-specific amperometric probe as described above.…”

Section: Methodsmentioning

confidence: 99%

Presence of the μ3 Opiate Receptor in Endothelial Cells

Stefano

Hartman

Bilfinger

et al. 1995

Journal of Biological Chemistry

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246

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Initial confinement of opiate receptors to the nervous system has recently been broadened to several other cell types. Based on the well established hypotensive effect of morphine, we hypothesized that endothelial cells may represent a target for this opiate substance. Endothelial cells (human arterial and rat microvascular) contain a high affinity, saturable opiate binding site presumed to mediate the morphine effects that is stereoselectively and characteristically antagonized by naloxone. This opiate alkaloid-specific binding site is insensitive to opioid peptides. It is, therefore, considered to be the same subtype of opiate receptor (designated 3 ) used in the mediation of morphine in other cell types exhibiting the same binding profile. Experiments with endothelial cultures and the aortic ring of rats cultured in vitro demonstrate that morphine exerts direct modulatory control over the activities of endothelial cells, which leads to vasodilation. It induces the production of nitric oxide, a process that is sensitive to naloxone antagonism and nitric oxide synthase inhibition. In contrast with that of opiates, the administration of opioid peptides does not induce nitric oxide production by endothelial cells. In conclusion, the data presented above reveal a novel site of morphine action, endothelial cells, where a 3 receptor is coupled to nitric oxide release and vasodilation.The vast majority of pharmacological studies of the properties of opiate substances have long been almost exclusively concerned with their effects on analgesic and antinociceptive phenomena. More recently, a number of experiments have demonstrated that morphine modulates the activity of varieties of cell types, among them the immunocytes of several mammalian and invertebrate species (1, 2). In addition, this largely down-regulating effect was found to be mediated by a highly specific, opiate alkaloid-sensitive receptor used selectively by opiates (1, 2). In the present case, the receptor ( 3 ) accomplishes this by counteracting the cellular responsiveness to a number of immunoexcitatory molecules, e.g. lipopolysaccharides and some cytokines (see Ref. 3).In this context, morphine was found to be quite potent in lowering or terminating the activation of human granulocytes and monocytes exposed to the stimulatory activity of plasma obtained from cardiopulmonary bypass patients (4 -7). From these observations, we surmised that a proportion of these cells may have been derived from intravascular immune cells whose adhesiveness to the vascular lining may have been altered by the presence of morphine in this tissue.The present study was aimed at the exploration of the possibility that endothelial cells may be under the direct control of the opiates. It provided evidence for the specific binding of morphine to endothelial cells, resulting in stimulation of nitric oxide (NO) 1 production in a naloxone-reversible manner and relaxation of blood vessels. It also demonstrated that these activities are mediated by the special opiate receptor 3 presen...

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Inhibitory effect of morphine on granulocyte stimulation by tumor necrosis factor and substance P

Cited by 26 publications

References 14 publications

Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute‐phase protein responses in patients undergoing cardiac surgery

Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute‐phase protein responses in patients undergoing cardiac surgery

Neutrophilia and granulocyte colony-stimulating factor levels after cardiopulmonary bypass

Presence of the μ3 Opiate Receptor in Endothelial Cells

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