The effect of midazolam and propofol on interleukin-8 from human polymorphonuclear leukocytes.
Anesthetics and sedatives contribute to postoperative immunosuppression. Interleukin-8 (IL-8) is a chemotactic and activating factor that mediates neutrophil adhesion and margination and is essential for host defense. We investigated the effect of anesthetics on isolated human polymorphonuclear leukocyte production of IL-8. Healthy human polymorphonuclear leukocytes were isolated using a single-step density gradient and stimulated with lipopolysaccharide in the presence of varying concentrations of propofol or midazolam for up to 20 h. IL-8 was measured in both culture supernatants and cell lysates using enzyme immunoassay, and IL-8 mRNA in cells was measured using Northern blotting and phosphorimaging. Data were analyzed using Kruskal-Wallis analysis of variance or the Mann-Whitney U-test as appropriate. Lipopolysaccharide increased extracellular accumulation of interleukin-8, which was suppressed by both propofol (P = 0.025) and midazolam (P = 0.028). However, intracellular IL-8 increased with exposure to lipopolysaccharide (P = 0.028) and remained increased with both anesthetics. Northern blot analysis also revealed increased IL-8 mRNA levels in the presence of both midazolam and propofol, which was confirmed by molecular imaging. These data strongly suggest that the anesthetics modulate transport or secretion of IL-8 protein from the cell. Suppression of IL-8 by anesthetics and sedatives may predispose postoperative and intensive care patients to infection.


CONCLUSIONS
Anesthesia causes immune suppression and alters neutrophil function. We investigated the effect of propofol and midazolam on interleukin-8, a neutrophil chemotactic agent in human neutrophils. Both anesthetics decreased extracellular interleukin-8 accumulation, but intracellular levels and mRNA remained high. This suggests that propofol and midazolam alter interleukin-8 secretion from cells.
Galley
H F
HF
Academic Unit of Anaesthesia and Intensive Care, University of Aberdeen, Scotland. h.f.galley@abdn.ac.uk
Dubbels
A M
AM
Webster
N R
NR
D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002630:Chemotactic Factors / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003422:Critical Care; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008874:Midazolam / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009894:Opportunistic Infections / Q000209:etiology; D011183:Postoperative Complications; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors
D018686:Anesthetics, Intravenous; D002630:Chemotactic Factors; D006993:Hypnotics and Sedatives; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D008874:Midazolam; D015742:Propofol