International immunopharmacology
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Int. Immunopharmacol. · Jan 2018
Generation of complement molecular complex C5b-9 (C5b-9) in response to poly-traumatic hemorrhagic shock and evaluation of C5 cleavage inhibitors in non-human primates.
Severe trauma initiates a systemic inflammatory cascade and that involves early activation of complement and cleavage of C5 into C5a (anaphylatoxin) and C5b (C5b-9 membrane attack complex). We examined activation of C5 in non-human primate (NHP) models of hemorrhagic shock. Blood plasma concentrations of C5b-9 were significantly increased in NHPs in response to hemorrhage alone and were further increased with the addition of tissue trauma. ⋯ Quidel's A217 antibody demonstrated dose-dependent inhibition of C5 cleavage and hemolysis in NHP samples, whereas LGM-Eculizumab only inhibited complement-mediated hemolysis in human samples. This study shows that complement activation in NHPs following experimental poly-traumatic hemorrhagic shock is consistent with clinical reports, and that cleavage of C5 and complement-mediated hemolysis can be effectively inhibited in vitro using a small peptide inhibitor. Taken together, these findings offer a clinically-relevant vehicle and a potential strategy for treatment of hemorrhagic shock with poly-traumatic injury.
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Int. Immunopharmacol. · Jan 2018
In contrast to morphine, buprenorphine enhances macrophage-induced humoral immunity and, as oxycodone, slightly suppresses the effector phase of cell-mediated immune response in mice.
Opioid receptors are commonly expressed on various immune cells, macrophages especially. Thus, these cells are prone to stimulation with opioids, which seems to be responsible for opioid-induced immunomodulatory effects. While morphine, fentanyl and methadone influence on mouse immune response was recently studied, little is known about the potential immunomodulatory impact of buprenorphine and oxycodone. ⋯ Current observations confirm that macrophages greatly contribute to immunomodulatory effects of opioids. Studies on immunomodulation by opioids have great importance related to the evaluation of its beneficial and adverse effects on patient condition. Our research showed that oxycodone exerts the weakest immunomodulatory properties, allowing us to assume this drug as safer than morphine during prolonged therapy.