Granulocyte Colony-Stimulating Factor Enhances Pulmonary Host Defenses in Normal and Ethanol-Treated Rats
The Journal of Infectious DiseasesPublished 1 November 1991
Sacha B. Nelson, W. R. Summer, G. J. Bagby, Celso Vataru Nakamura, L. Stewart, Gary Lipscomb
Citations149
SJR quartileQ1
SJR score2.04
SNIP1.23
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
G-CSF augmented the recruitment of PMNL into the lungs of control rats and significantly attenuated the adverse effects of ethanol on PMNL entry into the lung, and enhanced intrapulmonary bactericidal activity against this pathogen in normal and ethanol-treated rats.
Abstract
Ethanol suppresses functions of the polymorphonuclear leukocyte (PMNL), seriously compromising normal host defenses against pneumonia. Because granulocyte colony-stimulating factor (G-CSF) augments the number and function of PMNL, the effect of G-CSF on the antibacterial defenses of the lung in normal and acutely intoxicated rats was studied. Animals received G-CSF or vehicle twice a day for 2 days, then ethanol or saline, followed by challenge with Klebsiella pneumoniae. K. pneumoniae elicited an intrapulmonary influx of PMNL in control rats that was markedly suppressed by prior ethanol administration. G-CSF augmented the recruitment of PMNL into the lungs of control rats and significantly attenuated the adverse effects of ethanol on PMNL entry into the lung. G-CSF enhanced intrapulmonary bactericidal activity against this pathogen in normal and ethanol-treated rats. All intoxicated rats pretreated with the vehicle died, while greater than 90% of rats pretreated with G-CSF survived. These findings suggest a potential role for G-CSF in mitigating the adverse effects of ethanol on PMNL delivery and pulmonary host defenses.
Keywords
Immunology and MicrobiologyMedicine
ScienceThe Human Hematopoietic Colony-Stimulating Factors
1,688 Citations1987Steven C. Clark, Robert Kamen
These advances have led to a much better understanding of the role of the myeloid growth factors in regulating hematopoiesis in vivo that should soon find practical application in clinical medicine.
ScienceRecombinant Human Granulocyte Colony-Stimulating Factor: Effects on Normal and Leukemic Myeloid Cells
1,245 Citations1986L M Souza, Thomas C. Boone +13 more
Experiments were conducted to isolate and characterize the gene and gene product of a human hematopoietic colony-stimulating factor with pluripotent biological activities, which has the ability to induce differentiation of a murine myelomonocytic leukemia cell line WEHI-3B(D+) and cells from patients with newly diagnosed acute nonlymphocytic cancer.
JAMAAlcohol and Immune Defense
425 Citations1986Rob Roy MacGregor
The impact on health includes increased morbidity from cirrhosis, gastrointestinal hemorrhage, trauma, cancer, and infection, and factors that contribute to the high incidence of infection among alcoholics include dulled mental function, breakdown of local protective barriers, aspiration, exposure, and malnutrition.
The Journal of Experimental MedicineRecombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates.
420 Citations1987Karl Welte, Mary Ann Bonilla +7 more
A potential role for rhG-CSF is indicated in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation and the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis.
New England Journal of MedicineEffect of Alcohol and Various Diseases on Leukocyte Mobilization, Phagocytosis and Intracellular Bacterial Killing
347 Citations1970R. G. Brayton, Peter E. Stokes +2 more
Ethyl alcohol produced a profound depression in the rate of leukocyte mobilization into traumatized skin of nutritionally normal people, and was comparable to that observed in terminal phases of medical shock.
BloodLevels of serum granulocyte colony-stimulating factor in patients with infections
336 Citations1990Masaki Kawakami, Hisashi Tsutsumi +6 more
Medical Clinics of North AmericaInfections in the Alcoholic
244 Citations1984Harry C. Adams, Colin Jordan
Serious infections appear to occur more frequently in alcoholic patients, but whether this is due to the effects of alcohol per se or to the other frequent complications of alcoholism has not been determined.
The Journal of Infectious DiseasesThe Effects of Acute and Chronic Alcoholism on Tumor Necrosis Factor and the Inflammatory Response
237 Citations1989Sacha B. Nelson, G. J. Bagby +2 more
NatureGM-CSF induces human neutrophil IgA-mediated phagocytosis by an IgA Fc receptor activation mechanism
214 Citations1988Richard H. Weisbart, Amelia Kacena +2 more
A new mechanism for CSF-agumented host defence whereby neutrophil function can be modulated byCSF-mediated IgA Fc receptor activation is defined, which is associated with the development of IgA-mediated phagocytosis.
Biochemical and Biophysical Research CommunicationsRecombinant human granulocyte colony-stimulating factor enhances superoxide release in human granulocytes stimulated by the chemotactic peptide
201 Citations1987Seiichi Kitagawa, Akira Yuo +4 more
Findings indicate that G-CSF is a potent activator of mature granulocyte functions.
BloodHematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy
198 Citations1989A. Lindemann, F Herrmann +5 more
G-CSF appears to be an appropriate means to selectively increase the number of functionally competent polymorphonuclear phagocytes in patients with advanced malignancy.
MedicinePNEUMONIAS CAUSED BY GRAM NEGATIVE BACILLI
159 Citations1966James R. Tillotson, A. Martin Lerner
Infection and ImmunityProtective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice
158 Citations1987Masahiko Matsumoto, S Matsubara +6 more
It is shown that prophylactic therapy with hG-CSF may augment the resistance of immunocompromised patients to infections, and the same treatment was able to protect significantly against systemic infections caused by Serratia marcescens, Escherichia coli, Staphylococcus aureus, and Candida albicans.
Annals of Internal MedicineColony-Stimulating Factors and Host Defense
152 Citations1989Richard H. Weisbart, Judith C. Gasson +1 more
The results of studies of granulocyte-macrophage colony-stimulating factors in patients with the acquired immunodeficiency syndrome (AIDS) suggest a possible therapeutic role for colony- Stimulation factors in augmenting mechanism of host defense.
BloodEffect of acute alcohol intoxication on granulocyte mobilization and kinetics
115 Citations1978SJ Gluckman, R. R. MacGregor
Granulocyte mobilization into skin abrasions in human volunteers was significantly inhibited by acute alcohol intoxication, and protection of the abrasion against heat loss did not reduce the inhibited delivery in intoxicated volunteers.
The American Journal of the Medical SciencesALCOIIOL AS A FACTOR IN THE ILLNESS OF UNIVERSITY SERVICE PATIENTS
99 Citations1965James Nolan
A prospective study was conducted by the Medical House Staff of the Grace-New Haven Community Hospital in order to assess the magnitude of the role of alcohol in the illnesses of patients admitted to general medical wards, finding that one admission out of 10 is directly related to the abuse of alcohol.
The Journal of Infectious DiseasesEffect of Ethanol on Functions Required for the Delivery of Neutrophils to Sites of Inflammation
98 Citations1988Rob Roy MacGregor, M. Safford +1 more
Ethanol affects several neutrophil delivery functions normally activated by inflammatory stimuli, including Release of both primary and secondary granule contents after activation showed dose-dependent inhibition, whereas resting granule content and spontaneous release were unaffected.
Archives of Internal MedicinePharyngeal Flora in Ambulatory Alcoholic Patients
96 Citations1978Zelma Fuxench-López
The high prevalence and higher colonization rates of Gram-negative bacilli in alcoholic patients might explain the higher incidence of gram- negative bacillary pneumonia among alcoholics.
Annals of Internal MedicineRecurrent Pneumonia
93 Citations1969Richard H. Winterbauer, GEORGE A. BEDON +1 more
Pediatric ResearchProphylactic or Simultaneous Administration of Recombinant Human Granulocyte Colony Stimulating Factor in the Treatment of Group B Streptococcal Sepsis in Neonatal Rats
91 Citations1990Mitchell S. Cairo, Deborah Mauss +4 more
Preliminary data suggest that either simultaneous or prophylactic pulse administration of rhG-CSF may have a synergistic and protective effect on survival in antibiotic-treated experimental GBS in the neonatal rat.
Infection and ImmunityTherapeutic efficacy of granulocyte colony-stimulating factor alone and in combination with antibiotics against Pseudomonas aeruginosa infections in mice
80 Citations1990Hiromi Yasuda, Yoko Ajiki +5 more
The therapeutic efficacy of granulocyte colony-stimulating factor against an experimental intramuscular infection induced by Pseudomonas aeruginosa in mice was confirmed and the reduction in leukopenia by G-CSF remarkably strengthened the therapeutic effect of antibiotics in mice.
Infection and ImmunityIn vivo activation of neutrophil function in hamsters by recombinant human granulocyte colony-stimulating factor
79 Citations1988Arthur M. Cohen, De’Yana Hines +2 more
It is suggested that recombinant human granulocyte colony-stimulating factor may be a useful adjunct in the treatment of bacterial infections in neutropenic patients.
BloodGranulocyte- and granulocyte-macrophage colony-stimulating factors enhance neutrophil cytotoxicity toward HIV-infected cells
73 Citations1989GC Baldwin, ND Fuller +3 more
The findings regarding neutrophil ADCC in AIDS are clinically relevant because the availability of CSFs now permits therapeutic regulation of neutrophils in AIDS patients, and presumably natural antibody may be useful in targeting HIV-infected cells for neutrophIL cytotoxicity in vivo.
PubMedThe beneficial effect of granulocyte colony-stimulating factor (G-CSF) in combination with gentamicin on survival after Pseudomonas burn wound infection.
66 Citations1989Geoffrey M. Silver, R. L. Gamelli +1 more
The use of hematopoietic growth stimulants in combination with antibiotic therapy may result in improved outcome after burn injury, and it suggests new treatment options in the management of postburn infectious complications.
PubMedThe effect of ethanol on adherence and phagocytosis by rabbit alveolar macrophages.
62 Citations1980David Rimland, Hand Wl
Results suggest that inhibition of alveolar macrophage adherence and phagocytosis may be mediated by one or a combination of three mechanisms: osmolar forces altering the cell membrane, changes in cyctic nucleotide concentrations, or disruption of microtubules.
Experimental Biology and MedicineMechanism of Inhibition of Granulopoiesis by Ethanol
51 Citations1984Paul S. Imperia, G. Chikkappa +1 more
The results suggest that the neutropenia which occurs in relation to alcohol abuse may in part be related to decreased CSA production from T cells, as well as the mechanism of inhibition of neutrophilic granulopoiesis by ethanol.
PubMedMechanisms of ethanol-induced defects of alveolar macrophage function.
43 Citations1984David Rimland
The effect of ethanol on alveolar macrophages is probably complex, but changes in osmolarity and increases in cAMP levels, perhaps interrelated by some pertubation in the cell membrane, may explain the defect.
PubMedIntroduction and overview of hematopoietic growth factors.
42 Citations1989Gabrilove Jl
The CSFs and EPO have many potential clinical applications, including enhancing myeloid effector cell production and function, rendering malignant cells more susceptible to killing by cycle-specific agents, and correcting the anemia of end-stage renal disease.
Annals of Internal MedicineClinical Observations of Acute Friedländer Pneumonia
40 Citations1963F Manfredi, WALTER J. DALY +1 more
In recent years acute Gram-negative bacterial infections of the lung, among them Friedlander pneumonia, have received renewed attention, and the incidence and severity of these infections has increased.
The American Journal of MedicinePrevention of respiratory tract infection
39 Citations1984W. G. Johanson
Prevention of pneumonia by manipulation of the bacterial flora of the upper respiratory tract is an approach that warrants further investigation and is not clinically possible at this time.
Archives of Internal MedicineAlcohol, Immunosuppression, and the Lung
37 Citations1982John S. Bomalaski
The older clinical literature and the more recent basic science literature deal with the effects of alcohol—a not inconsequential fact considering that at least 10% of the authors' population are alcoholics and billions of dollars are lost each year as a direct result of alcoholism.
Drug and Alcohol DependenceAlcohol-related morbidity among older career navy men
31 Citations1982Douglas Kolb, E. K. Eric Gunderson
Hospital admission histories were compared for groups of Navy enlisted men identified as alcohol abusers or controls during the later years of their service careers and the greatest differences in rates of specific illness between abusers and controls were observed for cirrhosis of the liver and diseases of the pancreas.
PubMedCharacterization of the pulmonary inflammatory response to an anaerobic bacterial challenge.
22 Citations1986Steve Nelson, Barbara E. Laughon +4 more
Data demonstrate B. gingivalis causes marked inflammation in the lung that progresses to severe bronchopneumonia and lung abscess, and these data demonstrate the pulmonary antibacterial response to these organisms has not been well described.