OBJECTIVE: To investigate the influence of granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) on preimplantation development and implantation in mouse embryos. MATERIAL AND METHODS: Eight-cell stage mouse embryos were cultured for 96 hours with G-CSF or GM-CSF at concentrations of 10 pg/ml, 100 pg/ml, 1 ng/ml and 10 ng/ml. Embryos not treated with G-CSF or GM-CSF were served as control. The percentages of embryos which developed to expanded, hatched blastocyst stage and in vitro implantation at 96 hours were determined. Results were analyzed with Kolmogorov-Smirnov test and analysis of variance (ANOVA). The statistical significance was defined as p<0.05. RESULTS: The percentages of fully expanded blastocysts in all G-CSF and GM-CSF treatment groups were not significantly different from the control. The percentages of hatched blastocysts were significantly higher in 100 pg/ml and 10 ng/ml of G-CSF treatment group compared to the control (p<0.05, p<0.05, respectively). The percentages of hatched blastocysts were significantly lower in 1 ng/ml of GM-CSF treatment group compared to the control, 10 pg/ml, and 100 pg/ml of GM-CSF treatment group (p<0.05, p<0.05, p<0.05, respectively), and the percentages of hatched blastocysts were also significantly lower in 10 ng/ml of GM-CSF treatment group compared to the control and 100 pg/ml of GM-CSF treatment group (p<0.05, p<0.05, respectively). The percentages of implanted blastocysts in vitro were significantly higher following incubation with all concentrations of G-CSF compared to the control and, especially in 100 pg/ml and 10 ng/ml of G-CSF treatment groups compared to the control and other treatment groups. The percentages of implanted blastocysts in vitro were significantly higher in 10 pg/ml of GM-CSF treatment group than the control and 100 pg/ml of GM-CSF treatment groups (p<0.05, p<0.05, respectively). CONCLUSION: G-CSF and GM-CSF might influence on embryonic development and implantation in mouse embryos.
Animals ; Blastocyst ; Colony-Stimulating Factors* ; Embryonic Development ; Embryonic Structures* ; Female ; Granulocyte Colony-Stimulating Factor ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes* ; Mice* ; Pregnancy

BACKGROUND: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. METHODS: A carcinogen- induced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with gamma-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. RESULTS: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with gamma-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. CONCLUSION: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by gamma-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.
Animals ; Apoptosis ; Colony-Stimulating Factors* ; Colorectal Neoplasms ; Granulocyte-Macrophage Colony-Stimulating Factor ; Mice ; Mitomycin ; Vaccination ; Vaccines ; Zidovudine

Granulocyte macrophage-colony stimulating factor (GM-CSF) occupies a central position in the regulation of hematopoietic responses. GM-CSF not only signals proliferations of granulocyte-macrophage but also drives these cells into differentiation and activates mature cells of the GM-CSF sensitive lineage. Myelosuppression that is induced by M-VAC (methotrexate, vinblastine, doxorubicin, cisplatinum) chemotherapy brings many problems in successful treatment such as sepsis, dose reduction, delaying the schedule. Granulocyte-macrophage colony stimulating factor is introduced hopefully as a new solution for these problems. So we evaluated the efficacy and safety of GM-CSF in leukopenia induced by M-VAC chemotherapy in patients with urothelial cancer. GM-CSF was administered at 200ug subcutaneously in 10 M-VAC cycles of 6 patients on 5th and 6th day after M-VAC therapy. Sixteen cycles, by which only M-VAC chemotherapy was administered without GM-CSF. of the other 6 patients served as control group. Mean white blood cell count in peripheral blood at M-VAC 2nd day and 15th day was 5,630/mm3 and 4,240/mm3 in GM-CSF administered cycles, 6,58l/mm3and 3,613/mm3 in non GM-CSF administered cycles. There was no delayed cycle in administration of MTX and vinblastine at M-VAC 15th day in the cycles with GM-CSF. There was no significant side effects caused by GM- CSF. The result indicates that GM-CSF can be used safely and effectively against leukopenia after M-VAC chemotherapy of urothelial cancer.
Appointments and Schedules ; Colony-Stimulating Factors ; Doxorubicin ; Drug Therapy* ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes ; Humans ; Leukocyte Count ; Leukopenia* ; Sepsis ; Vinblastine

There is increasing evidence that airway epithelial cells, when exposed to various gas-derived air pollutants, play an important role in airway inflammation by releasing inflammatory cytokines. However, there is little information on air pollutant-induced cytokine expression at the tissue level and on the role of sulfur dioxide (SO2), one of the major ambient air pollutants, in cytokine production. We studied whether or not a low concentration of sulfur dioxide induces an increase in tissue expression of interleukin-4 (IL-4), interleukin-8 (IL-8), and granulocyte/macrophage colony stimulating factor (GM-CSF). After exposing surgically obtained normal human nasal turbinates to 0.05 ppm SO2 for one hour, we conducted specific immunohistochemical staining to assess the tissue expression of each cytokine. We found that the percent expression of IL-8 and GM-CSF in the surface epithelium was significantly higher in each SO2-exposed tissue than in the matched control tissue. However, there was no significant difference in the number of submucosal IL-4-positive cells between exposed and control specimens. These results suggest that exposure to a low concentration of SO2 increases airway inflammation, apparently by inducing an increase in the expression of GM-CSF and IL-8.
Air Pollutants ; Colony-Stimulating Factors ; Cytokines ; Epithelial Cells ; Epithelium ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Humans ; Inflammation ; Interleukin-4* ; Interleukin-8* ; Mucous Membrane* ; Nasal Mucosa ; Sulfur Dioxide* ; Sulfur* ; Turbinates*

Pulmonary alveolar proteinosis (PAP) is a rare condition that is treated using whole lung lavage. A recent study suggested that granulocyte-macrophage colony stimulating factor (GM-CSF) plays roles in both the pathogenesis and treatment of PAP. We present a 69-year-old man with PAP who deteriorated despite bilateral whole lung lavage; that said, his symptoms, chest X-ray findings, and pulmonary function test improved after GM-CSF inhalation therapy over 12 months. GM-CSF therapy is an effective treatment modality for PAP.
Aged ; Bronchoalveolar Lavage ; Colony-Stimulating Factors ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Inhalation ; Lung ; Pulmonary Alveolar Proteinosis ; Respiratory Function Tests ; Respiratory Therapy ; Thorax

PURPOSE: Neutrophils are central to the defences against bacterial infection, and in neonates the number of neutrophils are decreased due to inhibited production and phagocytic function. This induces high mortality rates in infants suffering from neonatal sepsis. Exogenous GM-CSF can increase the number of neutrophils and improve the phagocytic function. To establish the most cost effective dose of exogenous granulocyte-macrophage colony-stimulating factor in infected neonates, we divided infected patients into two groups. The serum level of granulocyte-macrophage colony stimulating factor, white blood cell count and absolute granulocyte count were compared. METHODS: This study included 22 infants with infection, admitted to the neonatal intensive care unit of Chungnam National University Hospital, between February 1998 and September 1999. Infected infants were divided into two treatment groups with exogenous GM-CSF 3 microgram/kg/day & 10 microgram/kg/day. The total WBC count, the absolute granulocyte count and the serum GM-CSF concentration of peripheral blood before use of GM-CSF, and those of 2nd, 5th and 7th day after use were compared. RESULTS: In 3 microgram/kg/day group, WBC count and the absolute granulocyte count and the serum GM-CSF concentration reached a peak after the 2nd injection of GM-CSF. In 10 microgram/kg/day group, the WBC count and the absolute granulocyte count increased gradually until 7th day. There was tendency for the total WBC counts, the absolute granulocyte count and the serum GM-CSF concentration of peripheral blood in 10 microgram/kg group to increase more than those of 3 microgram/kg group, after exogenous GM-CSF treatment. CONCLUSION: In neonates, we propose the exogenous GM-CSF treatment 10 microgram/kg/day as being more effective than 3 microgram/kg/day protocol, which is one of the safest and most effective methods to increase the total WBC count, the absolute granulocyte count and the serum GM-CSF concentration of peripheral blood.
Bacterial Infections ; Chungcheongnam-do ; Colony-Stimulating Factors ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes ; Humans ; Infant ; Infant, Newborn ; Intensive Care, Neonatal ; Leukocyte Count ; Leukocytes ; Mortality ; Neutrophils ; Sepsis

It has been reported that the stimulated T lymphocytes might secret a neutrophil survival factor. Thus the goal of study was to determine which molecules are the neutrophil survival factors secreted from the phytohaemagglutinin (PHA)-stimulated T lymphocytes. Human peripheral blood T lymphocytes and neutrophils were isolated by Ficoll-paque density sedimentation from heparinized blood of healthy adult donors. The purity of T lymphocytes and neutrophils were more than 90% and 95%, respectively. The maximal effective condition for the neutrophil viability-sustaining activity was 1 ug/ml af PHA in 12 hours incubation with T lymphocytes. The effect of PHA-stimulated T lymphocyte conditioned medium (TCM) on the neutrophils were used for the comparison with PHA-nonstimulated TCM or enriched medium alone. Neutrophil viability-sustaining activity with PHA-stimulated TCM for 24 hours incubation was significantly higher than other groups (85+/-11 vs 43+/-5 vs 916%; p<0.01). In the analysis of the primary data, the good candidates for the neutrophil viability-sustaining factor were granulocyte/monocyte colony stimulating factor (GM-CSF) and interleukin-8 (IL-8). They were used in the bioassay and antibody neutralization of cytokine activity. ...continue...
Adult ; Biological Assay ; Colony-Stimulating Factors ; Culture Media, Conditioned ; Granulocyte-Macrophage Colony-Stimulating Factor ; Heparin ; Humans ; Interleukin-8 ; Lymphocytes ; Neutrophils* ; T-Lymphocytes ; Tissue Donors

OBJECTIVE: Granulocyte-macrophage colony stimulating factors known to be secreted in murine and human reproductive tract. The development of human, bovine and murine embryos could be promoted by addition of GM-CSF in culture medium. However, the pregnancy and implantation rate of embryos cultured in GM-CSF have not been evaluated. The aim of this study was to assess the effect of GM-CSF in embryo development, pregnancy and implantation rate. METHODS: A total of 191 IVF cycles were divided into control and GM-CSF supplement group (control =96, GM-CSF=95). The embryos were cultured for three day with or without 2 ng/ml of recombinant human GM-CSF. The quality of embryo, developmental velocity, pregnancy and implantation rates were compared. RESULTS: There was no difference in age, number of gonadotropin ampules used, number of oocytes and fertilization. The number of ICSI cycle was higher in GM-CSF group. In GM-CSF group, G-1 grade embryos were the highest in proportion (56.4%), while G-2 grade embryos were highest (44.3%) in control group. The developmental velocity of embryos were not different between GM-CSF and control group. The pregnancy and implantation rates were significantly higher in GM-CSF group than control (47.4% vs. 33.3%, 17.0% vs. 11.1% respectively). CONCLUSION: By adding GM-CSF in culture medium, the quality of embryo, pregnancy and implantation rate could be improved.
Colony-Stimulating Factors ; Embryonic Development ; Embryonic Structures ; Female ; Fertilization ; Gonadotropins ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Humans* ; Oocytes ; Pregnancy ; Sperm Injections, Intracytoplasmic

BACKGROUND AND OBJECTIVES: Airway epithelial cells contribute to the pathogenesis of air disease by their interaction with inhalant pathogenic extracts. Airborne fungi interact with nasal epithelial cell and enhance the production of inflammatory cytokines. Glucocorticosteroids (GCs) have been used therapeutically for nasal polyps and allergic disease with potent anti-inflammatory effects. The purpose of this study was to investigate the inhibitory effect of GCs on fungi induced nasal epithelial cell activation. MATERIALS AND METHODS: The epithelial cells of nasal polyps were obtained from patients and stimulated with Alternaria. To evaluate the anti-inflammatory effects of GCs, Alternaria was pretreated with GCs (triamcinolone, dexamethasone, and budesonide) and cultured with epithelial cells. Interleukin-8 (IL-8) and granulocyte-macrophage colony stimulating factor (GM-CSF) were measured to determine the activation of epithelial cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) test for protease-activated receptors (PARs) mRNA expression in nasal epithelial cells were performed. RESULTS: Alternaria enhanced the production of IL-8 and GM-CSF from nasal epithelial cells. GCs inhibited the activation of nasal epithelial cells, but the PAR2 and PAR3 mRNA expression were not suppressed by GCs. CONCLUSION: These data suggest that GCs inhibit the production of chemical mediators by Alternaria, but anti-inflammatory effect of GCs are not associated with PARs.
Adrenal Cortex Hormones* ; Alternaria ; Colony-Stimulating Factors ; Cytokines ; Dexamethasone ; Epithelial Cells* ; Fungi ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Interleukin-8 ; Nasal Polyps* ; Receptors, Proteinase-Activated ; RNA, Messenger

Idiopathic pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by surfactant component accumulation in the alveolar space. Idiopathic PAP has recently been recognized as a autoimmune disease of impaired alveolar macrophage function caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). While whole lung lavage has been the standard treatment, not every patient shows a complete response. Subcutaneous injection or inhalation of GM-CSF is another promising treatment option for PAP. A 45-year-old patient visited our hospital for dyspnea, he was diagnosed as PAP and underwent whole lung lavage. Eighteen months later, the patient had not achieved complete remission in despite of initial response. After then he was administered with GM-CSF (5 microgram/kg/day, subcutaneous injection) for fivetimes a week during 2 months. Nine months later, the abnormal shadows in high-resolution computed tomography (HRCT) decreased and the patient fully recovered in forced vital capacity. After 60 months, the HRCT scan showed complete remission of PAP.
Autoantibodies ; Autoimmune Diseases ; Bronchoalveolar Lavage ; Colony-Stimulating Factors ; Dyspnea ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Inhalation ; Injections, Subcutaneous ; Lung ; Macrophages, Alveolar ; Middle Aged ; Pulmonary Alveolar Proteinosis ; Vital Capacity