Alterations of neutrophil responses to tumor necrosis factor alpha and interleukin-8 following human endotoxemia

Interleukin-8 (IL-8), a neutrophil chemoattractant and activating cytokine, has been implicated as a proinflammatory mediator in gram-negative sepsis. In vitro data support the notion of IL-8 as an endothelial adherence inhibitor. To evaluate this issue, we infused six volunteers with reference endotoxin and measured plasma levels of IL-8, neutrophil tumor necrosis factor alpha (TNF-alpha) receptors, TNF-alpha-induced adherence to fibronectin, and neutrophil chemotaxis to IL-8 and other attractants. We found that, at 3 h postinfusion, IL-8 but not TNF-alpha plasma levels were elevated. Neutrophils had shed L-selectin (mean channel fluorescence decrease, 79 +/- 9 to 49 +/- 7; P = 0.0625) and TNF-alpha receptors (decrease in number of receptors per cell, 1,596 +/- 340 to 574 +/- 93; P = 0.004). Cells were chemotactically desensitized to IL-8. TNF-alpha-induced adherence to fibronectin was suppressed from 69% +/- 5% of the phorbol myristate acetate response to 38% +/- 7% (P = 0.0154). These findings support the notion that release of IL-8 into the vascular space may be an in vivo mechanism for suppression of neutrophil accumulation at extravascular sites. L-Selectin loss would reduce the ability of neutrophils to adhere to activated endothelial cells. The specific loss of migratory response to IL-8 would impair neutrophil delivery to areas where IL-8 was the predominant chemoattractant. Loss of TNF-alpha-induced adherence to fibronectin would blunt those responses, including production of oxidants, capacitated by adherence.

[1]  L D Solem,et al.  Mechanisms of loss of human neutrophil chemotaxis following thermal injury. , 1987, The Journal of burn care & rehabilitation.

[2]  A. Fowler,et al.  Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. , 1991, The American review of respiratory disease.

[3]  T. Schall,et al.  Identification of a promiscuous inflammatory peptide receptor on the surface of red blood cells. , 1993, The Journal of biological chemistry.

[4]  T. Standiford,et al.  Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. , 1990, The Journal of clinical investigation.

[5]  C. Hack,et al.  Interleukin-8 in sepsis: relation to shock and inflammatory mediators , 1992, Infection and immunity.

[6]  P Hansell,et al.  L-selectin function is required for beta 2-integrin-mediated neutrophil adhesion at physiological shear rates in vivo. , 1992, The American journal of physiology.

[7]  R. Strieter,et al.  Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups , 1993, The Lancet.

[8]  M. Wewers,et al.  Alveolar fluid neutrophil elastase activity in the adult respiratory distress syndrome is complexed to alpha-2-macroglobulin. , 1988, The Journal of clinical investigation.

[9]  C. Nathan,et al.  Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins , 1989, The Journal of cell biology.

[10]  J. Gallin,et al.  Intravenous endotoxin recruits a distinct subset of human neutrophils, defined by monoclonal antibody 31D8, from bone marrow to the peripheral circulation. , 1989, Cellular immunology.

[11]  J. Kovacs,et al.  The cardiovascular response of normal humans to the administration of endotoxin. , 1989, The New England journal of medicine.

[12]  L. McIntire,et al.  Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro. , 1991, The Journal of clinical investigation.

[13]  B. Schleiffenbaum,et al.  The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation. , 1990, The Journal of clinical investigation.

[14]  F. Luscinskas,et al.  In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil-endothelial adhesive interactions. , 1992, Journal of immunology.

[15]  R. Strieter,et al.  Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection , 1992, Infection and immunity.

[16]  R. Tompkins,et al.  Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. , 1990, The Journal of infectious diseases.

[17]  H. Büller,et al.  Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. , 1990, Blood.

[18]  R. Strieter,et al.  Interleukin-8 as a macrophage-derived mediator of angiogenesis. , 1992, Science.

[19]  K. Matsushima,et al.  Properties of the novel proinflammatory supergene "intercrine" cytokine family. , 1991, Annual review of immunology.

[20]  M. A. Martin,et al.  Gram-negative sepsis and the adult respiratory distress syndrome. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  K. Tracey,et al.  Peripheral blood leukocyte kinetics following in vivo lipopolysaccharide (LPS) administration to normal human subjects. Influence of elicited hormones and cytokines. , 1989, Annals of surgery.

[22]  R. Schlesinger,et al.  Alveolar macrophage-stimulated neutrophil and monocyte migration: effects of in vitro ozone exposure. , 1988, Toxicology and applied pharmacology.

[23]  M. Gimbrone,et al.  Interleukin‐8 induces changes in human neutrophil actin conformation and distribution: relationship to inhibition of adhesion to cytokine‐activated endothelium , 1992, Journal of leukocyte biology.

[24]  H. D. Hochstein,et al.  The processing and collaborative assay of a reference endotoxin. , 1983, Journal of biological standardization.

[25]  M. Cybulsky,et al.  Intravascular IL-8. Inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation. , 1991, Journal of immunology.

[26]  S. Wright,et al.  Multiple receptors for endotoxin. , 1991, Current opinion in immunology.

[27]  I. Singer,et al.  Adhesomes: specific granules containing receptors for laminin, C3bi/fibrinogen, fibronectin, and vitronectin in human polymorphonuclear leukocytes and monocytes , 1989, The Journal of cell biology.

[28]  M. Brockhaus,et al.  Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia. , 1992, The Journal of clinical investigation.

[29]  J. Solomkin,et al.  Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of the adult respiratory distress syndrome in man. , 1985, Surgery.

[30]  M. Baggiolini,et al.  Neutrophil activation and the effects of interleukin-8/neutrophil-activating peptide 1 (IL-8/NAP-1). , 1992, Cytokines.

[31]  T. Standiford,et al.  Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. , 1991, Experimental lung research.

[32]  M. Cybulsky,et al.  Acute inflammation and microthrombosis induced by endotoxin, interleukin-1, and tumor necrosis factor and their implication in gram-negative infection. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[33]  M. Matthay,et al.  Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. , 1992, The American review of respiratory disease.

[34]  R. Spragg,et al.  Pathogenesis of the adult respiratory distress syndrome. Evidence of oxidant activity in bronchoalveolar lavage fluid. , 1983, The Journal of clinical investigation.

[35]  R. Bone,et al.  Modulators of coagulation. A critical appraisal of their role in sepsis. , 1992, Archives of internal medicine.

[36]  A. Huber,et al.  Regulation of transendothelial neutrophil migration by endogenous interleukin-8. , 1991, Science.

[37]  H. Tilg,et al.  Induction of circulating and erythrocyte-bound IL-8 by IL-2 immunotherapy and suppression of its in vitro production by IL-1 receptor antagonist and soluble tumor necrosis factor receptor (p75) chimera. , 1993, Journal of immunology.

[38]  M. Baggiolini,et al.  Neutrophil activating factor (NAF) induces polymorphonuclear leukocyte adherence to endothelial cells and to subendothelial matrix proteins. , 1989, Biochemical and biophysical research communications.

[39]  J. Solomkin,et al.  Characterization of N-formyl-methionyl-leucyl-phenylalanine receptors on human neutrophils. Effects of isolation and temperature on receptor expression and functional activity. , 1988, Journal of immunology.

[40]  E. Weibel,et al.  Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. , 2015, The American review of respiratory disease.

[41]  F. Luscinskas,et al.  Leukocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion. , 1991, Journal of immunology.

[42]  R. Senior,et al.  Proteolysis by neutrophils. Relative importance of cell-substrate contact and oxidative inactivation of proteinase inhibitors in vitro. , 1982, The Journal of clinical investigation.

[43]  J D Chambers,et al.  Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[44]  R. Senior,et al.  Extracellular matrix injury during lung inflammation. , 1987, Chest.

[45]  J. Solomkin,et al.  Regulation of TNF-α Receptor Expression on Human Neutrophils by Various Cell Activating Factors , 1994 .

[46]  P. Allen,et al.  A novel member of the integrin receptor family mediates Arg-Gly-Asp- stimulated neutrophil phagocytosis , 1989, The Journal of cell biology.

[47]  F. Ognibene,et al.  Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. , 1990, Annals of internal medicine.

[48]  L. Bignold,et al.  Inhibition of chemotaxis of neutrophil leukocytes to interleukin-8 by endotoxins of various bacteria , 1991, Infection and immunity.

[49]  S. Wright,et al.  Activation of the adhesive capacity of CR3 on neutrophils by endotoxin: dependence on lipopolysaccharide binding protein and CD14 , 1991, The Journal of experimental medicine.

[50]  W. Shoemaker,et al.  Effects of accidental trauma on cytokine and endotoxin production , 1993, Critical care medicine.

[51]  R. Danner,et al.  Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents , 1991, The Journal of experimental medicine.

[52]  S. Suter,et al.  High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. , 1992, The American review of respiratory disease.

[53]  B. Dewald,et al.  A novel neutrophil-activating factor produced by human mononuclear phagocytes , 1988, The Journal of experimental medicine.

[54]  Obin,et al.  Endothelial interleukin-8: a novel inhibitor of leukocyte-endothelial interactions. , 1989, Science.