Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury
Tóm tắt
Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-α (TNF-α), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean ±SD 2717 ±2421 μl−1 preoperatively) peaked 60 min after declamping the aorta at 7432 ±4357 μl−1 (P < 0.01) and remained elevated 7136 ±5194 μl−1 at 180 min (P < 0.01). Plasma GEL level (168 ±71 μg sd L−1 preoperatively) peaked at 1134 ±453 μg · L−1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 ±467 μg · L−1, after 180 min (P < 0.01). Serum IL-6 level (118 ±59 pg · ml−1 preoperatively) peaked at 436 ±143 pg · ml−1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 ±109 pg · ml−1, after 180 min. Serum IL-8 level (37 ±44 pg · ml−1 preoperatively) peaked at 169 ±86 pg · ml−1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 ±78 pg · ml−1 180 min after declamping of the aorta. Serum TNF-α was decreased at 60 min after aortic occlusion but otherwise did not change. Plasma GEL concentrations correlated with serum IL-8 levels (R = 0.7, P = 0.001) and the IL-6 and IL-8 concentrations correlated with the duration of aortic clamping (R = 0.64, P = 0.01, R = 0.7, P = 0.01). We conclude that the increases of IL-6 and IL-8 occur as a result of ischaemia, and suggest that these cytokines participate in reperfusion injury by activating neutrophils.
Tài liệu tham khảo
Romson JL, Hook BG, Kunkel SL, Abrams GD, Schork MA, Lucchesi BR. Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation 1983; 67: 1016–23.
Mullane KM, Read N, Salmon JA, Moncada S. Role of leukocytes in acute myocardial infarction in anesthetized dogs: relationship to myocardial salvage by antiinflammatory drugs. J Pharmacol Exp Ther 1984; 228: 510–22.
Ida N, Sakurai S, Hosoi K, Kunitomo T. A highly sensitive enzyme-linked immunosorbent assay for the measurement of interleukin-8 in biological fluids. J Immunol Methods 1992; 156: 27–38.
Ida N, Sakurai S, Hosaka T, et al. An enzyme-linked immunosorbent assay for the measurement of human interleukin-6. J Immunol Methods 1990; 133: 279–84.
Mullane KM, Moncada S. The salvage of ischemic myocardium by BW 755C in anaesthetized dogs. Prostaglandins 1982; 24: 255–66.
Lawrence MB, Springer TA. Leukocytes roll on a selection at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 1991; 65: 859–73.
Shröder JM, Mrowietz U, Morita E, Christophers E. Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. J Immunol 1987; 139: 3474–83.
Peveri P, Walz A, Dewald B, Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med 1988; 167: 1547–59.
Schröder JM. The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil archidonate-5-lipoxygenase, but not the release of cellular arachidonate. J Exp Med 1989; 170: 847–63.
Paccaud JP, Shifferli JA, Baggiolini M. NAP-l/IL-8 induces up-regulation of CR1 receptors in human neutrophil leukocytes. Biochem Biophys Res Comm 1990; 166: 187–92.
Detmers PA, Lo SK, Olsen-Egbert E, Walz A, Baggiolini M, Cohn ZA. Neutrophil-activating protein 1/ interleukine-8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. J Exp Med 1990; 171: 1155–62.
Endo S, Inada S, Yamashita N, Hoshi S, Yoshida M, Ceska M. Polymorphonuclear leukocyte elastase and plasma interleuken 8 levels in patients with ARDS. Journal of the Japanese Association for Acute Medicine. 1992; 3: 92.
Matsushima K, Morishita K, Yoshimura T, et al. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med 1988; 167: 1883–93.
Larsen CG, Anderson AP, Oppenheim JJ, Matsushima K. Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumor necrosis factor. Immunology 1989; 68: 31–6.
Strieter RM, Kunkel SL, Showell HJ, et al. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-a, LPS, and IL-lβ. Science 1989; 243: 1467–9.
Metinko A, Kunkel S, Standiford T, Streter R. Monocyte expression of interleukin-8 in response to oxidant stress. FASEB J abstracts part 1 1991: 1941 A704.
Horii Y, Muraguchi A, Suematsu S, et al. Regulation of BSF-2/IL-6 production by human mononuclear cells: macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol 1988; 141: 1529–35.
Matsuzaki N, Saji F, Kameda T, et al. In vitro and in vivo production of interleukin-6 by fetal mononuclear cells. Clin Immunol Immunopathol 1990; 55: 305–14.
Hirano T, Kishimoto T. Interleukin 6. In: Sporn MB, Roberts AB (Eds.). Handbook of Experimental Pharmacology vol. 95/1 “Peptide Growth Factors and Their Receptors.” Berlin: Springer-Verlag 1990; 633–65.
Weiss SJ, Curnutte JT, Regiani S. Neutrophil-mediated solubilization of the subendothelial matrix: oxidative and nonoxidative mechanisms of proteolysis used by normal and chronic granulomatous disease phagocytes. J Immunol 1986; 136: 636–41.
Kusner DJ, King CH. Protease-modulation of neutrophil Superoxide response. J Immunol 1989; 143: 1696–702.
Peveri P, Walz A, Dewald B, Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med 1988; 167: 1547–59.
Mukaida N, Shiroo M, Matsusima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol 1989; 143: 1366–71.
Standiford TJ, Strieter RM, Chensue SW, Westwick J, Kasahara K, Kunkel SL. IL-4 inhibits the expression of IL-8 from stimulated monocytes. J Immunol 1990; 145: 1435–9.