Plasma levels of the chemokines monocyte chemotactic proteins-1 and -2 are elevated in human sepsis.

Because of their effects on monocytes, monocyte chemotactic proteins-1 and -2 (MCP-1 and MCP-2) may participate in the pathophysiology of sepsis. We measured circulating MCP-1 and MCP-2 levels in 42 septic patients having positive local or blood cultures. MCP-1 and MCP-2 levels were elevated in 24 (57%) and 25 (59%) of 42 septic patients, respectively, compared with healthy volunteers. Both patients with gram-positive and gram-negative infections had elevated MCP-1 plasma levels (P = .0001) and P < .0001), respectively; Mann-Whitney-U test), whereas patients with gram-positive infection, but not those with gram-negative infection, had increased MCP-2 plasma levels (P= .0182). No relative differences in MCP-1 and MCP-2 plasma levels were observed between several subgroups of patients (sepsis v septic shock; survivors v nonsurvivors), although levels of MCP-1 were the highest in patients with the more severe forms of sepsis, ie, those with shock or a lethal outcome. Serial observations showed that MCP-1 and MCP-2 plasma levels remained elevated for at least 48 hours. MCP-1 correlated weakly with interleukin-8 and MCP-2, the correlations for which were most pronounced in patients with septic shock. MCP-2 correlated with interleukin-8, and surprisingly, with the complement activation product C3a; these correlations further improved when analyzing patients with septic shock or when applying gram-positive infections. Thus, our results not only show increased MCP-1 and MCP-2 levels in patients with sepsis, but also suggest that the synthesis and release of MCP-1 and MCP-2 in sepsis are differently regulated in part.

[1]  C. Hack,et al.  Monocyte chemotactic protein 1 is released during lethal and sublethal bacteremia in baboons. , 1995, The Journal of infectious diseases.

[2]  D. Pittet,et al.  The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. , 1995, JAMA.

[3]  G. Opdenakker,et al.  Induction of monocyte chemotactic proteins MCP-1 and MCP-2 in human fibroblasts and leukocytes by cytokines and cytokine inducers. Chemical synthesis of MCP-2 and development of a specific RIA. , 1994, Journal of immunology.

[4]  R. Horuk The interleukin-8-receptor family: from chemokines to malaria. , 1994, Immunology today.

[5]  F. Meloni,et al.  Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. , 1994, American journal of respiratory and critical care medicine.

[6]  T. Standiford,et al.  The immunopathology of chemotactic cytokines: the role of interleukin-8 and monocyte chemoattractant protein-1. , 1994, The Journal of laboratory and clinical medicine.

[7]  K. Matsushima,et al.  Protection against lethal bacterial infection in mice by monocyte-chemotactic and -activating factor , 1994, Infection and immunity.

[8]  R. Danner,et al.  Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. Effects of intravenous lipopolysaccharide on free attractants, specific IgG autoantibodies and immune complexes. , 1993, Journal of immunology.

[9]  M. Burdick,et al.  Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. , 1992, The Journal of clinical investigation.

[10]  G. Opdenakker,et al.  Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family , 1992, The Journal of experimental medicine.

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

[12]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[13]  R. Colman,et al.  Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis. , 1992, The Journal of laboratory and clinical medicine.

[14]  A. Billiau,et al.  Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock , 1991, European journal of clinical investigation.

[15]  B. Rollins,et al.  Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes. , 1991, Blood.

[16]  C. Dinarello Interleukin-1 and interleukin-1 antagonism. , 1991, Blood.

[17]  A. D. de Vos,et al.  Sensitive ELISA for interleukin-6. Detection of IL-6 in biological fluids: synovial fluids and sera. , 1991, Journal of immunological methods.

[18]  Robert C. Thompson,et al.  Interleukin-1 receptor antagonist reduces mortality from endotoxin shock , 1990, Nature.

[19]  C. Hack,et al.  Activation of the complement system during immunotherapy with recombinant IL-2. Relation to the development of side effects. , 1990, Journal of immunology.

[20]  M. Baggiolini,et al.  Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. , 1989, The Journal of clinical investigation.

[21]  L. G. Thijs,et al.  Increased plasma levels of interleukin-6 in sepsis [see comments] , 1989 .

[22]  J. Schröder,et al.  The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate , 1989, The Journal of experimental medicine.

[23]  H. Buller,et al.  ENDOTOXAEMIA: AN EARLY PREDICTOR OF SEPTICAEMIA IN FEBRILE PATIENTS , 1988, The Lancet.

[24]  J. Schröder,et al.  Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. , 1987, Journal of immunology.

[25]  E. J. Young,et al.  Manifestations of sepsis. , 1987, Archives of internal medicine.

[26]  W. R. Mccabe,et al.  Gram-negative bacteremia: IV. Re-evaluation of clinical features and treatment in 612 patients , 1980 .

[27]  C. Hack,et al.  Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery. , 1995, American journal of respiratory and critical care medicine.

[28]  J. Damme Interleukin-8 and related chemotactic cytokines , 1994 .

[29]  S. Calvano,et al.  Cytokine Markers of the Human Response to Sepsis , 1994 .

[30]  E. Leonard,et al.  Human monocyte chemoattractant protein-1 (MCP-1). , 1990, Immunology today.

[31]  C. Hack,et al.  Elevated plasma levels of the anaphylatoxins C3a and C4a are associated with a fatal outcome in sepsis. , 1989, The American journal of medicine.

[32]  L A Aarden,et al.  Increased plasma levels of interleukin-6 in sepsis. , 1989, Blood.

[33]  B. Beutler,et al.  The role of cachectin/TNF in endotoxic shock and cachexia. , 1988, Immunology today.

[34]  A. Cerami,et al.  Cachectin (Tumor Necrosis Factor) , 1988 .