TY - JOUR AU - Metcalf, D AB - SUMMARY To determine whether circulating levels of any of the cotony-stimulating factors (CSF) might contribute to the host response in severe sepsis, plasma concentrations of granulocyte CSF (GCSF), granulocyte-macrophage CSF (GM-CSF), and macrophage CSF (M-CSF), were measured by immunoassays in 20 subjects with meningococcaemia, a bloodstream infection caused by Neisseria meningitidis, that has proven to be a valuable model to study the responses of other inflammatory mediators during sepsis and septic shock in humans. Plasma G-CSF concentrations were transiently elevated in most subjects during the early phase of meningococcaemia, and were higher in subjects with septic shock (mean ± s.d. = 165± 142 ng/ml, n = 9) compared with those who remained normotensive (mean ± s.d.=7±2ng/ml, ng/ml, n=10) (p<005). Peak plasma G-CSF concentrations >10ng/ml were associated with the development of septic shock (P<0.01), disseminated intravascular coagulation (p<0.01). fulminant infection (P<0.05), and a fatal outcome (p<0.01). Plasma GM-CSF concentrations > 1 ng/ml were briefly present in subjects with life-threatening septic shock (1–15 ng/ml, n = 5). and were strongly associated with fulminant meningococcaemia (P <0.01). Plasma M-CSF concentrations were marginally elevated in all subjects, but were not associated with complications related to or arising from sepsis-induced organ injury. This study demonstrates that plasma levels of G-CSF, GM-CSF and M-CSF show very different responses during meningococcaemia, changes which presumably reflect the different roles played by these mediators in sepsis and, potentially, in septic shock. colony-stimulating factor, cytokines, meningococcaemia, sepsis, septic shock References 1 Metcalf D. Control of granulocytes and macrophages; molecular, cellular, and clincal aspects . Science 1991 ; 254 : 529 – 33 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Layton JE. Granulocyte colony-stimulating factor: structure, function and physiology . Growth Factors 1992 : 6 : 179 – 86 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Gasson JC. Molecular physiology of granulocyte-macrophage colony-stimulating factor . Blood 1991 ; 77 : 1131 – 45 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Zimmerman JJ , Ringer TV. Inflammatory host response in sepsis . Crit Care Clin 1992 ; 8 : 163 – 89 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Deitch EA. Multiple organ failure: pathophysiology and potential future therapy , Ann Surg 1992 : 216 : 117 – 34 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Foster R , Metcalf D, Robinson WA, Bradley TR. Bone marrow colony stimulating activity in human sera . Brit J Haematol 1968 ; 15 : 147 – 59 . Google Scholar Crossref Search ADS WorldCat 7 Metcalf D , Wahren B. Bone marrow colony stimulating activity of sera in infectious mononucleosis , Brit Med J 1968 ; 3 : 99 – 101 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Cheers C , Haigh AM, Kelso A, Melcalf D, Stanley ER, Young AM. Production of colony-stimulating factors (CSFs) during infection: separate determinations of macrophage-, granulocyte-. granulocyte- macrophage and multi-CSF's . Infect Immun 1988 : 56 : 247 – 51 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Metcalf D. Induction of differentiation in murine myelomonocytic leukemia cells by the serum of patients with acute myeloid leukemia and other diseases . Int J Cancer 1981 ; 27 : 577 – 84 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Cebon J , Layton JE, Maher D, Morstyn G. Endogenous haemopoietic growth factors in neutropenia and infection . Br J Haematol 1994 ; 86 : 265 – 74 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Watari K , Asano S, Shirafuji N et al. Serum granulocyte colonystimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay . Blood 1989 ; 73 : 117 – 22 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Kawakami , M. Tsutsumi H, Kumakawa T et al. Levels of serum granulocyte colony-stimulating factors in patients with infections . Blood 1990 ; 76 : 1962 – 4 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Waage A , Haistensen A, Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease . Lancet 1987 ; i : 355 – 7 . Google Scholar OpenURL Placeholder Text WorldCat 14 Waage A , Brandtzaeg P, Haistensen A, Kierulf P, Espevik T. The complex pattern of cylokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome . J Exp Med 1989 ; 169 : 333 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Girardin E , Grau GE, Dayer J-M, Roux-Lombard P , the JS Study Group, Lamberl P-H. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura . New Eng J Med 1988 ; 319 : 397 – 400 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Halslensen A , Ceska M, Brandtzaeg P, Redl H, Naess A, Waage A. lnterleukin-8 in serum and cerebrospinal fluid from pateints with meningococcal disease , J Infect Dis 1993 ; 167 : 471 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Derkx B , Marchant A, Goldman M, Bijimer R. van Deventer S. High levels of inlerleukin-10 during the initial phase of fulminant meningococcal septic shock . J infect Dis 1995 ; 171 : 229 – 32 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Waring PM , Waring LJ, Metcalf D. Circulating leukemia inhibitory factor levels correlate with disease severity in meningococcemia . J Infect Dis 1994 ; 170 : 1224 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Campbell IK , Novak U, Cebon J, Layton JE, Hamilton JA. Human articular cartilage and chrondrocytes produce hematopoietic colony-stimulating factors in culture in response to IL I . J Immunol 1991 ; 147 : 1238 – 46 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 20 Layton JE , Hockman H, Sheridan WP, Morstyn G. Evidence for a novel in vivo control mechanism of granulopoiesis: mature cellrelated control of a regulatory growth factor . Blood 1989 ; 74 : 1303 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Cebon JS , Dempsey P, Fox R, Kannourakis G, Bonnem E, Burgess AW, Morstyn G. Pharmokinetics of human granulocyte-macrophage colony stimulating factor (hGM-CSF) using a sensitive immunoassay . Blood 1988 ; 72 : 1340 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 22 Taveira da Silva AM , Kaulbach HC, Chuidian FS, Lambert DR, Suffredini AF, Danner RL. Shock and multiple organ dysfunction after self-administration of Salmonella endotoxin . N Engl J Med 1993 ; 328 : 1457 – 60 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Brandlzaeg P , Kierulf P, Gaustad P et al. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease , J Infect Dis 1989 ; 159 : 195 – 204 . Google Scholar Crossref Search ADS PubMed WorldCat 24 Morstyn G , Lieschke , GJ, Sheridan W, Layton J, Cebon J, Fox RM. Clinical experience with recombinant human granulocyte colony-stimulating factor and granutocyte macrophage colonystimulating factor . Semin Hematol 1989 ; 26 ( Suppl. 2 ): 9 – 13 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 25 Kanazawa M , Ishizaka A, Hasegawa N, Suzuki Y, Yokoyama T. Granulocyte colony-stimulating factor does not enhance endoloxininduced acute lung injury in guinea pigs . Am Rev Resp Dis 1993 : 145 : 1030 – 5 . Google Scholar Crossref Search ADS WorldCat 26 Havill AM , Andersen JW, Korach E, Nelson S. Enhancement of endoloxin-induced lethality in the mouse by GM-CSF . Am Rev Respir Dis 1991 : 143 ( Suppl. ): 236 (abstr). Google Scholar PubMed OpenURL Placeholder Text WorldCat 27 Fink MP , O'Sullivan BP, Menconi MJ et al. Effect of granulocyte colony-stimulating factor on systemic and pulmonary responses to endotoxin in pigs . J Trauma 1993 ; 34 : 571 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 28 Koizumi T , Kubo K, Shinozaki S, Koyama S, Kobayashi T, Sekiguchi M. Grunulocyte colony-stimulating factor does not exacerbate endotoxin-induced lung injury in sheep . Am Rev Resp Dis 1993 ; 148 : 132 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 29 Görgen , I , Hartung T, Leist M et al. Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaceharideinduced toxicity via suppression of systemic tumor necrosis factorα . J Immunol 1992 ; 149 : 918 – 24 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 30 Toda H , Murata A, Matsuura N et al. Therapeutic efficacy of granulocyte colony-stimulating factor against rat cecal ligation and puncture model . Stem Cells 1993 ; 11 : 228 – 34 . Google Scholar Crossref Search ADS PubMed WorldCat 31 O'Reilly M , Silver GM, Greenhaigh DG, Gamelli RL, Davis JH, Hebert JC. Treatment of intra-abdominal infection with granulocyte colony-stimulating factor . J Trauma 1992 ; 33 : 679 – 82 . Google Scholar Crossref Search ADS PubMed WorldCat 32 Eichacker PQ , Waisman Y, Natanson C et al. Recombinant human granulocyte colony-stimulating factor reduces endotoxemia and improves cardiovascular function and survival during bacterial sepsis in non-neutropenic canines , Clin Res 1993 : 41 : 240 (Abstr.). Google Scholar OpenURL Placeholder Text WorldCat 33 Simms HH , D'Amico R. Granulocyte colony-stimulaling factor reverses septic shock-induced polymorphonuclear leukocyte dysfunction . Surgery 1994 ; 115 : 85 – 93 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 34 Sissons SD , Dinareilo CA. Production of interleukin-lα, and interleukin-1β and tumor necrosis factor by human mononuclear cells stimulated with granulocyte-macrophage colony-stimulating factor . Blood 1988 ; 72 : 1368 – 74 . Google Scholar Crossref Search ADS PubMed WorldCat 35 Heidenreich S , Gong J-H, Schmidt A, Nain M, Diethard G. Macrophage activation by granulocyte/macrophage colony stimulating factor . J Immunol 1989 ; 143 : 1198 – 205 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 36 Tiegs G , Barsig J, Matiba B, Uhlig S, Wendel A. Potentiation by granulocyte macrophage colony-stimulating factor of lipopolysaccharide toxicity in mice . J Clin Invest 1994 : 93 : 2616 – 22 . Google Scholar Crossref Search ADS PubMed WorldCat 37 Granowitz EV , Porat R, Orencole SF et al. Granulocyte-macrophage colony-stimulating factor synthesis during experimental endotoxemia in humans . J Infect Dis 1992 ; 166 : 1204 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 38 Verhoef G , Boogaerts M. Treatment with granulocyte-macrophage colony stimulating factor and the adult respiratory distress syndrome . Am J Hematol 1991 ; 36 : 285 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 39 Antman KS , Griffin JD, Elias A et al. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy- induced myelosuppression . N Engl J Med 1988 : 319 : 593 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 40 Maekensen A , Galanos C, Wehr U, Engelhardt R. Endotoxin tolerance: regulation of cytokine production and cellular changes in response to endotoxin application in cancer patients . Euro Cytokine Netw 1992 ; 3 : 571 – 9 . Google Scholar OpenURL Placeholder Text WorldCat 41 Mangan KF , Mullancy MT, Diaz Barrientos T, Kernan NA. Serum interleukin -3 levels following autologous or allogeneic bone marrow transplantation: effects of T-cell depletion, blood stem cell infusion, and hematopoietic growth factor treatment . Blood 1993 ; 8l : 19l5 – 22 . Google Scholar OpenURL Placeholder Text WorldCat 42 Meeker TC , Hardy D, Willman C, Hogan T, Abrams J. Activation of the interleukin-3 gene by chromosomal translocation in acute lymphocytic leukemia with eosinophilia . Blood 1990 ; 76 : 285 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 43 Lieschke GJ , Grail D, Hodgson G et al. Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization . Blood 1994 ; 84 : 1737 – 46 . Google Scholar Crossref Search ADS PubMed WorldCat 44 Stanley E , Lieschke GJ, Grail D et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology . Proc Natl Acad Sci USA 1994 ; 91 : 5592 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 45 Dranoff G , Crawford AD, Sadelain M et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis . Science 1994 ; 264 : 713 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 46 Basu S , Marino M, Savoia H et al. Increased tolerance to endotoxin by granulocyte macrophage colony stimulating (GM-CSF) factor deficient mice . Blood 1994 ; 84 ( Suppl. 1 ): 510a (Abstr.). Google Scholar OpenURL Placeholder Text WorldCat 47 Wiktor-Jedrzejczak W , Ansari AA, Szperl M, Urbanowska E. Distinct in vivo functions of two macrophage subpopulations as evidenced by studies using macrophage-deficient op/op mouse . Eur J Immunol 1992 ; 22 : 1951 – 4 . Google Scholar Crossref Search ADS PubMed WorldCat This content is only available as a PDF. © 1995 Blackwell Science Ltd This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) TI - Differential alterations in plasma colony-stimulating factor concentrations in meningococcaemia JO - Clinical & Experimental Immunology DO - 10.1111/j.1365-2249.1995.tb03844.x DA - 2008-06-28 UR - https://www.deepdyve.com/lp/oxford-university-press/differential-alterations-in-plasma-colony-stimulating-factor-XOu0bIEygs SP - 501 EP - 506 VL - 102 IS - 3 DP - DeepDyve ER -