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Infect Immun. Jan 1995; 63(1): 104–109.
PMCID: PMC172964

Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of patients with bacterial infections.


To investigate the physiological role of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adaptation mechanisms of myelopoiesis to enhanced demand, we studied both cytokines and their myeloid target cells in hematologically healthy patients suffering from acute bacterial infections. Endogenous serum levels of G-CSF and GM-CSF, granulocyte-macrophage colony-forming cell (GM-CFC) concentrations, and differential counts were determined for the peripheral blood of 57 patients with clinically apparent bacterial infections (26 males and 31 females aged 16 to 89 years) and 18 healthy controls (8 males and 10 females aged 23 to 84 years). Patients were selected for acute-phase protein and at least two additional clinical signs reflecting a bacterial infection. Patients showed significantly higher numbers of myeloid progenitor cells than controls (median, 68 versus 26 GM-CFC/ml; P < or = 0.01). G-CSF but not GM-CSF levels were found to be elevated (> or = 50 to 863 pg/ml). In the acute stage of infection, progenitor and cytokine levels were not influenced by gender, differences in therapy, or localization of the infection. Progenitor and G-CSF levels were not associated with absolute neutrophil counts or C-reactive protein. However, a negative correlation between number of GM-CFC per milliliter and age (R = -0.47; P < or = 0.001) and an inverse relationship between the incidence of high GM-CFC concentrations and elevated G-CSF levels (phi = -0.34; P < or = 0.01) were found. Combining both parameters into a cytokine-progenitor pattern, we observed a highly significant age-dependent response of myelopoiesis to inflammation (P < or = 0.001). Younger patients had high progenitor counts (> 75 GM-CFC/ml) associated with G-CSF levels below 50 pg/ml, whereas for the older patients, the reverse pattern was predominant. The results indicate that the age-dependent myelopoietic response to acute bacterial infections is characterized by an inverse relationship between progenitor cells and G-CSF. The observed cytokine-progenitor patterns could have implications for therapy with G-CSF and the prognosis of infectious diseases.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Antman KS, Griffin JD, Elias A, Socinski MA, Ryan L, Cannistra SA, Oette D, Whitley M, Frei E, 3rd, Schnipper LE. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced myelosuppression. N Engl J Med. 1988 Sep 8;319(10):593–598. [PubMed]
  • Calandra T, Baumgartner JD, Grau GE, Wu MM, Lambert PH, Schellekens J, Verhoef J, Glauser MP. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J Infect Dis. 1990 May;161(5):982–987. [PubMed]
  • Cannistra SA, Griffin JD. Regulation of the production and function of granulocytes and monocytes. Semin Hematol. 1988 Jul;25(3):173–188. [PubMed]
  • Cheers C, Haigh AM, Kelso A, Metcalf D, Stanley ER, Young AM. Production of colony-stimulating factors (CSFs) during infection: separate determinations of macrophage-, granulocyte-, granulocyte-macrophage-, and multi-CSFs. Infect Immun. 1988 Jan;56(1):247–251. [PMC free article] [PubMed]
  • Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Lond) 1990 Aug;79(2):161–165. [PubMed]
  • DeLamarter JF. Hemopoietic colony stimulating factors. A physiological and pharmacological role in fighting infection? Biochem Pharmacol. 1988 Aug 15;37(16):3057–3062. [PubMed]
  • Dörmer P, Hültner L, Mergenthaler HG. Proliferation and maturation of human bone marrow cells in infectious diseases. Pathol Res Pract. 1990 Feb;186(1):145–149. [PubMed]
  • Hyde SR, McCallum RE. Lipopolysaccharide-tumor necrosis factor-glucocorticoid interactions during cecal ligation and puncture-induced sepsis in mature versus senescent mice. Infect Immun. 1992 Mar;60(3):976–982. [PMC free article] [PubMed]
  • Kawakami M, Tsutsumi H, Kumakawa T, Abe H, Hirai M, Kurosawa S, Mori M, Fukushima M. Levels of serum granulocyte colony-stimulating factor in patients with infections. Blood. 1990 Nov 15;76(10):1962–1964. [PubMed]
  • Kawakami M, Tsutsumi H, Kumakawa T, Hirai M, Kurosawa S, Mori M, Fukushima M. Serum granulocyte colony-stimulating factor in patients with repeated infections. Am J Hematol. 1992 Nov;41(3):190–193. [PubMed]
  • Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (1). N Engl J Med. 1992 Jul 2;327(1):28–35. [PubMed]
  • Mackensen A, Galanos C, Engelhardt R. Treatment of cancer patients with endotoxin induces release of endogenous cytokines. Pathobiology. 1991;59(4):264–267. [PubMed]
  • MacVittie TJ, Monroy RL, Patchen ML, Souza LM. Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. Int J Radiat Biol. 1990 Apr;57(4):723–736. [PubMed]
  • McCarthy DM, Goldman JM. Transfusion of circulating stem cells. Crit Rev Clin Lab Sci. 1984;20(1):1–24. [PubMed]
  • Metcalf D. The role of the colony-stimulating factors in resistance to acute infections. Immunol Cell Biol. 1987 Feb;65(Pt 1):35–43. [PubMed]
  • Mertelsmann R, Herrmann F, Hecht T, Schulz G. Hematopoietic growth factors in bone marrow transplantation. Bone Marrow Transplant. 1990 Aug;6(2):73–77. [PubMed]
  • Morstyn G, Campbell L, Souza LM, Alton NK, Keech J, Green M, Sheridan W, Metcalf D, Fox R. Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet. 1988 Mar 26;1(8587):667–672. [PubMed]
  • Nothdurft W, Selig C, Fliedner TM, Hintz-Obertreis P, Kreja L, Krumwieh D, Kurrle R, Seiler FR, Weinsheimer W. Haematological effects of rhGM-CSF in dogs exposed to total-body irradiation with a dose of 2.4 Gy. Int J Radiat Biol. 1992 Apr;61(4):519–531. [PubMed]
  • Omori F, Okamura S, Shimoda K, Otsuka T, Harada M, Niho Y. Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions. Biotherapy. 1992;4(2):147–153. [PubMed]
  • Rothstein G. Hematopoiesis in the aged: a model of hematopoietic dysregulation? Blood. 1993 Nov 1;82(9):2601–2604. [PubMed]
  • Rothstein G, Christensen RD, Nielsen BR. Kinetic evaluation of the pool sizes and proliferative response of neutrophils in bacterially challenged aging mice. Blood. 1987 Dec;70(6):1836–1841. [PubMed]
  • Sallerfors B, Olofsson T, Lenhoff S. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum in bone marrow transplanted patients. Bone Marrow Transplant. 1991 Sep;8(3):191–195. [PubMed]
  • Sashida M. [Mechanism of stimulation of spleen mononuclear cells by gram-positive bacterial peptidoglycan]. Nichidai Koko Kagaku. 1989 Sep;15(3):196–206. [PubMed]
  • Shirafuji N, Asano S, Matsuda S, Watari K, Takaku F, Nagata S. A new bioassay for human granulocyte colony-stimulating factor (hG-CSF) using murine myeloblastic NFS-60 cells as targets and estimation of its levels in sera from normal healthy persons and patients with infectious and hematological disorders. Exp Hematol. 1989 Feb;17(2):116–119. [PubMed]
  • Watari K, Asano S, Shirafuji N, Kodo H, Ozawa K, Takaku F, Kamachi S. Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay. Blood. 1989 Jan;73(1):117–122. [PubMed]
  • Whetton AD, Dexter TM. Myeloid haemopoietic growth factors. Biochim Biophys Acta. 1989 Dec 17;989(2):111–132. [PubMed]
  • Williams ME, Quesenberry PJ. Hematopoietic growth factors. Hematol Pathol. 1992;6(3):105–124. [PubMed]

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