Morphine-Sparing Effect by COX-1 Inhibitor Sustains Analgesic Function without Compromising Antigen-Specific Immunity and Antitumor Effect of Naked DNA Vaccine

Abstract

Morphine and ketorolac, two analgesics with different mechanisms, have been widely used in controlling cancer pain and postoperative pain in surgery. Our previous study revealed that morphine could suppress the anti-tumor effect of antigen-specific DNA vaccine. In this study, we further evaluated and compared another analgesic drug, ketorolac, with morphine for its analgesic functions and the antitumor immunities of antigen-specific DNA vaccine. We first observed that ketorolac-treated mice did not enhance tumorigenesis nor suppress the anti-tumor effects of antigen-specific (calreticulin linked to HPV16 E7) CRT/E7 DNA vaccine. We then demonstrated that ketorolac was less potent in inducing apoptosis of T lymphocytes and the generation of reactive oxygen species, in reducing mitochondrial membrane potentials, and leading to the activation of caspases 3 and 7 in T lymphocytes than morphine. When CRT/E7 DNA vaccinated mice treated with ketorolac, the declines of frequencies of E7-specific IFN-y-secreting CD8+ T cell precursors were slower in the morphine-treated group. CRT/E7 DNA vaccinated mice, treated with a mixture of morphine and ketorolac, could maintain the analgesic function without experiencing a decrease in the anti-tumor effects. CRT/E7 DNA vaccine with the opioid-sparing effect of ketorolac could provide potent anti-tumor effects and good analgesic function.

The Reasons for Higher Mortality Rate in Opium Addicted Patients with COVID-19: A Narrative Review

“…Morphine could inhibit chemokine-mediated immune cells migration in response to pathogen infection (44). Interestingly, morphine alters the CD4 + and CD8 + of T cell subsets (45,46). CD4 + T cells of patients taking morphine after operation for pain control are decreased (47).…”

Inflammatory Markers: Serum Amyloid A, Fibrinogen and C-Reactive Protein — A Revisited Study

“…IL-6 exhibits pleiotropic biological functions and is produced by a variety of cell types, including monocyteslmacrophages, fibroblasts, endothelial cells and epithelial cells. IL-6 alone was capable of inducing synthesis of these two acute-phase proteins as well as fibrinogen and other cytokines, including interleukin-l (IL-l), tumour necrosis factor alpha, interferon gamma, transforming growth factor 15, leukaemia inhibitory factor, interleukin-ll and oncostatin M, and also modulating synthesis of acute-phase proteins (65)(66). These cytokines can act independently or, as is often the case, interact with each other and other extracellular signals, such as hormones, resulting in the production of specific patterns of acute-phase proteins.…”

Cholesterol: An Inflammatory Compound

“…Human plaque analysis has revealed that MMP-9 is catalytically active and may thus contribute to the dysregulation of extracellular matrix that leads to plaque rupture during the complication of atherothrombosis (23)(24)(25)(26). Further evidence suggests that local overexpression of MMP-9 promotes intravascular thrombus formation through increased tissue factor expression and tissue factor-mediated activation of the coagulation cascade (27)(28)(29)(30) These data support an important role for MMP-9 in several stages of atherosclerosis.…”