title: Early alterations in the number of circulating lymphocyte subpopulations and enhanced proinflammatory immune response during opioid-based general anesthesia.
abstract: The balance between proinflammatory and anti-inflammatory processes is of key importance in the reaction of the body to infection, injury, and surgical trauma. Drugs commonly used in anesthesia and intensive care may modulate immunological reactions by influencing intercellular communication through modification of cytokine response and fluctuation of peripheral immune cells such as natural killer (NK) cells, B cells, and T lymphocyte subpopulations (CD4+ and CD8+ cells). To examine the effects of general anesthesia with the hypnotic agent propofol and the opioid fentanyl, 30 patients undergoing minor elective orthopedic surgery were studied before and 20 min after application of the anesthetic drugs, but before the start of surgery. We found a significant enhancement of TNF-alpha and IL-1beta release in lipopolysaccharide (LPS)-stimulated whole blood cultures after induction of anesthesia. Similar results were observed with interferon-gamma (IFN-gamma) in cultures stimulated with phytohemagglutinin (PHA). Conversely, synthesis of the anti-inflammatory cytokine interleukin 10 (IL-10) decreased significantly in LPS-stimulated cultures. During general anesthesia, we found a decrease of circulating lymphocytes, characterized by a significant increase in the percentage of T lymphocytes in favor of CD4+ cells, increased B lymphocytes, and a significant decrease of NK cells. These data suggest that anesthesia with propofol and fentanyl promotes proinflammatory immune responses and influences peripheral lymphocyte composition in patients, which may subsequently affect pathophysiological processes during opioid-based anesthesia.
authors.affiliation: Institute of Immunology and Transfusion Medicine, University of Lübeck, 23538 Lübeck, Germany. brand@immu.mu-luebeck.de
authors.forename: Jörg-Matthias
authors.initials: JM
authors.lastname: Brand
authors.forename: Christoph
authors.initials: C
authors.lastname: Frohn
authors.forename: Jürgen
authors.initials: J
authors.lastname: Luhm
authors.forename: Holger
authors.initials: H
authors.lastname: Kirchner
authors.forename: Peter
authors.initials: P
authors.lastname: Schmucker
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000768:Anesthesia, General; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D005260:Female; D005283:Fentanyl / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D005283:Fentanyl