ArticleAnesthesia and analgesia2019
Suppression of Human Natural Killer Cells by Different Classes of Opioids.
Article in Anesthesia and analgesia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Pooled it
- Interventional factors influencing natural killer cell immunity in colorectal cancer: a systematic review.Cancer immunology, immunotherapy : CII · 2025Pooled it
- Effect of combined epidural-general anesthesia on long-term survival of patients with colorectal cancer: a meta-analysis of cohort studies.International journal of colorectal disease · 2022Pooled it
- Impact of opioid-free general anesthesia with locoregional blocks during breast cancer surgery on systemic inflammatory response: results from a randomized controlled trial.Regional anesthesia and pain medicine · 2026Trial
- Interpectoral and Pectoserratus Plane Block vs. Local Anesthetic Infiltration for Partial Mastectomy: A Prospective Randomized Trial.Pain research & management · 2024Trial
- Neutrophil-to-Lymphocyte Ratio as an Indicator of Opioid-Induced Immunosuppression After Thoracoscopic Surgery: A Randomized Controlled Trial.Journal of pain research · 2022Trial
- Comparison between epidural and intravenous analgesia effects on disease-free survival after colorectal cancer surgery: a randomised multicentre controlled trial.British journal of anaesthesia · 2021Trial
- Influence of exogenous opioids on the acute inflammatory response in the perioperative period of oncological surgery: a clinical study.Brazilian journal of anesthesiology (Elsevier)Trial
- Maternal opioid use disorder and hepatitis C infection in pregnancy reshape the peripheral immune landscape at term.EBioMedicine · 2026Article
- Single cell RNA transcriptome response to fentanyl use in persons with HIV infection.Scientific reports · 2026Article
- Perioperative local anesthetics as modulators of tumor progression and metastasis.Frontiers in pharmacology · 2026Review
- Research progress on the impact of opioids on the tumor immune microenvironment (Review).Molecular and clinical oncology · 2025Review
- Buprenorphine's Effect on the Human Immune System and Inflammation.Clinical and translational science · 2025Review
- The effect of concomitant drugs on oncological outcomes in patients treated with immunotherapy for metastatic urothelial carcinoma: a narrative review.Oncology research · 2025Review
- Opioids and Cancer: Current Understanding and Clinical Considerations.Current oncology (Toronto, Ont.) · 2024Review
- Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review.International journal of molecular sciences · 2024Review
- Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data.Journal of cancer research and clinical oncology · 2024Article
- Effect of Intraoperative Opioid Dose on Perioperative Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio in Glioma.Journal of inflammation research · 2024Article
- An Observational Study on Chronic Pain Biomarkers in Fibromyalgia and Osteoarthritis Patients: Which Role for Mu Opioid Receptor's Expression on NK Cells?Biomedicines · 2023Article
- Prevalence of COVID-19 outcomes in patients referred to opioid agonist treatment centers.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe use of regional and other opioid-sparing forms of anesthesia has been associated with a decrease in the recurrence of certain malignancies. Direct suppression of human natural killer cells by opioids has been postulated to explain this observation. However, the effect of different classes of opioids on suppression of natural killer cell cytotoxicity has not been systematically characterized.
methodsAfter confirming that freshly isolated natural killer cells from peripheral human blood express opioid receptors, cells were incubated with increasing concentrations of clinically used or receptor-specific opioid agonists. We also evaluated the effect of pretreatment with receptor-specific antagonists or naloxone. Treated natural killer cells were then coincubated with a carboxyfluorescein succinimidyl ester-labeled target tumor cell line, K562. Annexin V staining was used to compare the percent of tumor cell apoptosis in the presence of opioid-pretreated and untreated natural killer cells. Treated samples were compared to untreated samples using Kruskal-Wallis tests with a post hoc Dunn correction.
resultsMorphine, methadone, buprenorphine, loperamide, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin, and U-50488 significantly decreased natural killer cell cytotoxicity. When natural killer cells were pretreated with naloxone, cyprodime, and nor-binaltorphimine before exposure to morphine, there was no difference in natural killer cytotoxicity, compared to the amount observed by untreated natural killer cells. Fentanyl, O-desmethyltramadol, and [D-Pen2,D-Pen5] enkephalin did not change natural killer cell cytotoxicity compare to untreated natural killer cells.
conclusionsIncubation of isolated natural killer cells with certain opioids causes a decrease in activity that is not observed after naloxone pretreatment. Suppression of natural killer cell cytotoxicity was observed with μ- and κ-receptor agonists but not δ-receptor agonists. These data suggest that the effect is mediated by μ- and κ-receptor agonism and that suppression is similar with many clinically used opioids.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.