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August 1990, Vol 125, No. 8 >
ARTICLE | August 1990

Protective Effect of Recombinant Human Granulocyte Colony-Stimulating Factor Against Pneumococcal Infections in Splenectomized Mice FREE

James C. Hebert, MD; Michael O'Reilly; Richard L. Gamelli, MD
[+] Author Affiliations

Accepted for publication January 5, 1990.

Presented as a poster exhibit at the Ninth Annual Meeting of the Surgical Infection Society, Denver, Colo, April 13-14, 1989.

Reprint requests to Department of Surgery, University of Vermont College of Medicine, Given Building, Burlington, VT 05405 (Dr Hebert).


Arch Surg. 1990;125(8):1075-1078. doi:10.1001/archsurg.1990.01410200141022
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• Granulocyte colony-stimulating factor stimulates the proliferation and differentiation of progenitor cells committed to the neutrophil lineage, and it has been shown to improve survival to bacterial challenge in neutropenic mice. We studied recombinant human granulocyte colony-stimulating factor (rhG-CSF), cloned from bladder cell carcinoma line 5637, in a nonneutropenic infection model of Streptococcus pneumoniae pulmonary infection in splenectomized and sham-operated control mice. The rhG-CSF improved survival in the splenectomized mice but not in the sham-operated mice. Circulating leukocyte counts were greatest for the rhG-CSF—treated splenectomized mice compared with all other groups, presumably due to a loss of splenic sequestration. Clearance of live pneumococci from mouse lung pairs was impaired after splenectomy. The rhG-CSF improved lung clearance in both splenectomized and sham-operated mice compared with saline solution—treated controls. The number of live pneumococci recovered from tracheobronchial lymph nodes at 24 hours after aerosol challenge was greatest in the splenectomized mice vs sham-operated mice. Decreased numbers of viable pneumococci were recovered from tracheobronchial lymph nodes from the rhG-CSF—treated splenectomized mice and the sham-operated mice vs saline solution—treated controls. The rhG-CSF may be a useful adjuvant for treating infections in individuals with immunologic dysfunctions other than neutropenia.

(Arch Surg. 1990;125:1075-1078)

REFERENCES

1 +
Clark SC, Kamen R.  The human hematopoietic colony-stimulating factors . Science . 1987;;236:1229-1237.
2 +
Metcalf D.  The role of the colony-stimulating factors in resistance to acute infections . Immunol Cell Biol . 1987;;65(pt 1):35-43.
3 +
Metcalf D, Nicola NA.  Proliferative effects of purified granulocyte colony-stimulating factor (G-CSF) on normal mouse hemopoietic cells . J Cell Physiol . 1983;;116:198-206.
4 +
Platzer E, Welte K, Gabrilove J, et al.  Biological activities of human pluripotent hemopoietic colony-stimulating factor on normal and leukemic cells . J Exp Med . 1985;;162:1788-1801.
5 +
Souza LM, Boone TC, Gabrilove J, et al.  Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells . Science . 1986;;232:61.
6 +
Welte K, Platzer E, Lu E, et al.  Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factors . Proc Natl Acad Sci USA . 1985;;82:1526.
7 +
Platzer E, Oez S, Welte K, et al.  Human pluripotent hemopoietic colony stimulating factor: activities on human and murine cells . Immunobiology . 1986;;172:185.
8 +
Matosumoto M, Matsurbara S, Matsuno T, et al.  Protective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice . Infect Immun . 1987;;55:2715-2720.
9 +
Mooney DP, Gamelli RL, O'Reilly M, Hebert JC.  Recombinant human granulocyte colony-stimulating factor and Pseudomonas burn wound sepsis . Arch Surg . 1988;;123:1353-1357.
10 +
Hebert JC.  Pulmonary antipneumococcal defenses after hemisplenectomy . J Trauma . 1989;;29:1217-1221.
11 +
Hebert JC, Coil JA.  Increased susceptibility to pulmonary infection in alloxandiabetic mice . J Surg Res . 1981;;31:337-342.
12 +
Dickerman JD.  Bacterial infection and the asplenic host: a review . J Trauma . 1976;;16:662-668.
13 +
Coil JA, Dickerman JD, Bolton E.  Increased susceptibility of splenectomized mice to infection after exposure to an aerosolized suspension of type III Streptococcus pneumoniae . Infect Immun . 1978;;21:412-416.
14 +
Hebert JC, Gamelli RL, Dickerman JD, Chalmer BJ, Gump DW, Foster RS.  Lack of protection by pneumococcal vaccine after splenectomy in mice challenged with aerosolized pneumococci . J Trauma . 1983;;23:1-6.
15 +
Livingston DC, Levine BA, Sirinek KR.  Protection from pulmonary sepsis afforded by splenic autotransplantation . Surg Forum. 1982;;33:31-32.
16 +
Likhite VV.  Opsonin and leukophilic γ-globulin in chronically splenectomized rats with and without leterotopic autotransplanted splenic tissue . Nature . 1975;;253:742-744.
17 +
Boggart D, Biggar WD, Good RA.  Impaired intravascular clearance of pneumococcus type III following splenectomy . J Reticuloendothel Soc . 1972;;11:77-87.
18 +
Brown EJ, Hosea SW, Frank MM.  The role of the spleen in experimental pneumococcal bacteremia . J Clin Invest . 1981;;67:975-982.
19 +
Cioffi WG, Hebert JC, Gamelli RL, Foster RS.  The quantity and function of pulmonary alveolar macrophages after splenectomy and Corynebacterium parvum . J Trauma . 1985;;25:405-409.
20 +
Lau HT, Handy MA, Aetman RP.  Decreased pulmonary alveolar macrophage bactericidal activity in splenectomized rats . J Surg Res . 1983;;34:568-571.
21 +
Shennib H, Chiu RC, Mulder SD.  The effects of splenectomy and splenic implantation on alveolar macrophage function . J Trauma . 1983;;23:7-12.
22 +
Welte K, Bonilla MA, Gillio AP, et al.  Recombinant human granulocyte colony-stimulating factor: effects on hematopoiesis in normal and cyclophosphamide-treated primates . J Exp Med . 1987;;165:941-948.
23 +
Zsebo KM, Cohen AM, Murdock DC, et al.  Recombinant human granulocyte colony stimulating factor: molecular and biologic characterization . Immunogiology . 1986;;172:175.
24 +
Goldstein E, Lippert W, Warshouer D.  Pulmonary alveolar macrophage: defender against bacterial infection of the lung . J Clin Invest . 1974;;54:519-528.
25 +
Pierce AK, Reynolds RC, Harris G.  Leukocytic response to inhaled bacteria . Am Rev Respir Dis . 1977;;116:679-684.
26 +
Rehm SR, Gross GN, Pierce AK.  Early bacterial clearance from murine lungs: species-dependent phagocytic response . J Clin Invest . 1980;;66:194-199.
27 +
Toews GB, Gross GN, Peirce AK.  The relationship of inoculum size to lung bacterial clearance and phagocytic cell response in mice . Am Rev Respir Dis . 1979;;120:559-566.

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1 +
Clark SC, Kamen R.  The human hematopoietic colony-stimulating factors . Science . 1987;;236:1229-1237.
2 +
Metcalf D.  The role of the colony-stimulating factors in resistance to acute infections . Immunol Cell Biol . 1987;;65(pt 1):35-43.
3 +
Metcalf D, Nicola NA.  Proliferative effects of purified granulocyte colony-stimulating factor (G-CSF) on normal mouse hemopoietic cells . J Cell Physiol . 1983;;116:198-206.
4 +
Platzer E, Welte K, Gabrilove J, et al.  Biological activities of human pluripotent hemopoietic colony-stimulating factor on normal and leukemic cells . J Exp Med . 1985;;162:1788-1801.
5 +
Souza LM, Boone TC, Gabrilove J, et al.  Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells . Science . 1986;;232:61.
6 +
Welte K, Platzer E, Lu E, et al.  Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factors . Proc Natl Acad Sci USA . 1985;;82:1526.
7 +
Platzer E, Oez S, Welte K, et al.  Human pluripotent hemopoietic colony stimulating factor: activities on human and murine cells . Immunobiology . 1986;;172:185.
8 +
Matosumoto M, Matsurbara S, Matsuno T, et al.  Protective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice . Infect Immun . 1987;;55:2715-2720.
9 +
Mooney DP, Gamelli RL, O'Reilly M, Hebert JC.  Recombinant human granulocyte colony-stimulating factor and Pseudomonas burn wound sepsis . Arch Surg . 1988;;123:1353-1357.
10 +
Hebert JC.  Pulmonary antipneumococcal defenses after hemisplenectomy . J Trauma . 1989;;29:1217-1221.
11 +
Hebert JC, Coil JA.  Increased susceptibility to pulmonary infection in alloxandiabetic mice . J Surg Res . 1981;;31:337-342.
12 +
Dickerman JD.  Bacterial infection and the asplenic host: a review . J Trauma . 1976;;16:662-668.
13 +
Coil JA, Dickerman JD, Bolton E.  Increased susceptibility of splenectomized mice to infection after exposure to an aerosolized suspension of type III Streptococcus pneumoniae . Infect Immun . 1978;;21:412-416.
14 +
Hebert JC, Gamelli RL, Dickerman JD, Chalmer BJ, Gump DW, Foster RS.  Lack of protection by pneumococcal vaccine after splenectomy in mice challenged with aerosolized pneumococci . J Trauma . 1983;;23:1-6.
15 +
Livingston DC, Levine BA, Sirinek KR.  Protection from pulmonary sepsis afforded by splenic autotransplantation . Surg Forum. 1982;;33:31-32.
16 +
Likhite VV.  Opsonin and leukophilic γ-globulin in chronically splenectomized rats with and without leterotopic autotransplanted splenic tissue . Nature . 1975;;253:742-744.
17 +
Boggart D, Biggar WD, Good RA.  Impaired intravascular clearance of pneumococcus type III following splenectomy . J Reticuloendothel Soc . 1972;;11:77-87.
18 +
Brown EJ, Hosea SW, Frank MM.  The role of the spleen in experimental pneumococcal bacteremia . J Clin Invest . 1981;;67:975-982.
19 +
Cioffi WG, Hebert JC, Gamelli RL, Foster RS.  The quantity and function of pulmonary alveolar macrophages after splenectomy and Corynebacterium parvum . J Trauma . 1985;;25:405-409.
20 +
Lau HT, Handy MA, Aetman RP.  Decreased pulmonary alveolar macrophage bactericidal activity in splenectomized rats . J Surg Res . 1983;;34:568-571.
21 +
Shennib H, Chiu RC, Mulder SD.  The effects of splenectomy and splenic implantation on alveolar macrophage function . J Trauma . 1983;;23:7-12.
22 +
Welte K, Bonilla MA, Gillio AP, et al.  Recombinant human granulocyte colony-stimulating factor: effects on hematopoiesis in normal and cyclophosphamide-treated primates . J Exp Med . 1987;;165:941-948.
23 +
Zsebo KM, Cohen AM, Murdock DC, et al.  Recombinant human granulocyte colony stimulating factor: molecular and biologic characterization . Immunogiology . 1986;;172:175.
24 +
Goldstein E, Lippert W, Warshouer D.  Pulmonary alveolar macrophage: defender against bacterial infection of the lung . J Clin Invest . 1974;;54:519-528.
25 +
Pierce AK, Reynolds RC, Harris G.  Leukocytic response to inhaled bacteria . Am Rev Respir Dis . 1977;;116:679-684.
26 +
Rehm SR, Gross GN, Pierce AK.  Early bacterial clearance from murine lungs: species-dependent phagocytic response . J Clin Invest . 1980;;66:194-199.
27 +
Toews GB, Gross GN, Peirce AK.  The relationship of inoculum size to lung bacterial clearance and phagocytic cell response in mice . Am Rev Respir Dis . 1979;;120:559-566.

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