Serum Levels of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in a Group of Patients with Systemic Sclerosis

Author(s):  
A. Riccio ◽  
M. De Caterina ◽  
D. Natale ◽  
E. Grimaldi ◽  
G. Pronesti ◽  
...  

In this report we investigate the behaviour of the serum levels of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in the course of Systemic Sclerosis (SS). This cytokine is produced mainly by T and NK cells, and its possible role in the pathogenesis of SS has not been previously described in the literature. Serum GM-CSF levels were assayed in 10 female patients, ageing from 35 to 70, affected by SS. These patients were not suffering from other disorders and were not being treated with steroids or immunosuppressive drug. A solid phase immunoenzymatic method was used to assess the serum levels of GM-CSF. Reference values were previously determined in a control group of 36 healthy women blood donors (19 premenopausal and 17 postmenopausal) (x̄=20.1 ±12.3 pg/ml). All the patients but one showed significantly increased serum levels of GM-CSF (x̄= 120.9 ±125.5 pg/ml). The highest levels were found in the two oldest patients, who also had the longest clinical history of SS, but a clear correlation with age, disease duration or clinical manifestations was not evident, even if the postmenopausal age group patients showed a higher mean value of GM-CSF (x̄= 148.0±144.1 pg/ml) than that found in the premenopausal age group (x̄= 57.7±1.4 pg/ml) (in contrast with the findings in the control group). The absence of other pathogenic conditions in our patients suggests that the increase in serum levels of GM-CSF might be linked to the fibroblast proliferation which is typical of SS. However, our results do not explain the role played by this factor in the fibroblastic proliferation process and an in vitro study is necessary to clarify this aspect.

2018 ◽  
pp. 1-6
Author(s):  
Neemat M. Kassem ◽  
Alya M. Ayad ◽  
Noha M. El Husseiny ◽  
Doaa M. El-Demerdash ◽  
Hebatallah A. Kassem ◽  
...  

Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine stimulates growth, differentiation, and function of myeloid progenitors. We aimed to study the role of GM-CSF gene expression, its protein, and antibodies in patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) and their correlation to disease behavior and treatment outcome. The study included 50 Egyptian patients with AML/MDS in addition to 20 healthy volunteers as control subjects. Patients and Methods Assessment of GM-CSF gene expression was performed by quantitative real-time polymerase chain reaction. GM-CSF proteins and antibodies were assessed by enzyme-linked immunosorbent assay. Results There was significant decrease in GM-CSF gene expression ( P = .008), increase in serum level of GM-CSF protein ( P = .0001), and increase in anti–GM-CSF antibodies ( P = .001) in patients with AML/MDS compared with healthy control subjects. In addition, there was a significant negative correlation between serum levels of GM-CSF protein and initial peripheral blood blasts, percentage as well as response to therapy. Conclusion Any alteration in GM-CSF gene expression could have implications in leukemogenesis. In addition, GM-CSF protein serum levels could be used to predict outcome of therapy. GM-CSF antibodies may also play a role in the pathogenesis of AML/MDS. The use of these GM-CSF parameters for disease monitoring and as markers of disease activity needs further research.


2020 ◽  
Vol 15 (2) ◽  
pp. 131-136
Author(s):  
Diego Fiume ◽  
Ilaria Lenci ◽  
Martina Milana ◽  
Tommaso M. Manzia ◽  
Renato Massoud ◽  
...  

Background: Multiple biological functions have been recognized regarding Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Stem Cell Factor (SCF). Aim: To evaluate the serum changes of GM-CSF and SCF in patients undergoing surgical resection for liver tumor, in the regenerative phase after surgery in order to identify the possible relationship with the patient, tumor or surgical variables. Methods: Thirty-two consecutive patients (50% male, median age 66), undergoing hepatic resection of liver neoplasm, were evaluated. The liver tumor was Hepatocellular Carcinoma (HCC) in 44% of cases. Other tumors were cholangiocarcinoma and metastasis. Serum levels of GM-CSF and SCF were assessed at baseline and 2 days, 7 days and 4 weeks after surgery. Personal and clinical patient data were also recorded. The statistical analysis was carried out using t-test for unpaired data or ANOVA (repeated measure) for continuous variables and Fisher test for discrete variables. Results: GM-CSF levels remained constant after surgery and were compared to baseline values. SCF levels, on the other hand, increased during the time, after surgery. The evaluation of SCF levels (fold increase) according to surgical, patient and tumor variables evidenced some differences. At day 7 and week 4, SCF levels were statistically increased: i) in patients undergoing a large resection in comparison with others (p<0.05); ii) in patients non-cirrhotic in comparison with cirrhotic ones (p=0.02) and finally; iii) in patients with non-HCC tumor in comparison with HCC ones (p=0.02). Conclusions: During liver regeneration in humans, SCF serum levels are increased allowing to hypothesize a possible role of this chemokine during tissue growth and remodeling.


2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Nancy F Crum-Cianflone ◽  
Pamela V Lam ◽  
Sarah Ross-Walker ◽  
Lindsey B Rosen ◽  
Steven M Holland

Abstract Cryptococcus gattii infections, especially including those with severe clinical manifestations, may be related to underlying host immunologic factors. We present 2 cases with autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF), a key cytokine in macrophage function. Immunologic evaluation for anti-GM-CSF antibodies may be important to inform management and counseling.


Author(s):  
Barbara Mroczko ◽  
Maciej Szmitkowski ◽  
Urszula Wereszczyńska-Siemiątkowska ◽  
Grażyna Jurkowska

AbstractHematopoietic cytokines (HCs) can affect the growth and spread of cancer. Therefore, in the present study, we investigated in pancreatic cancer patients the serum levels of selected HCs, such as stem cell factor (SCF), interleukin 3 (IL-3), granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) in relation to a control group and to a group of patients with chronic pancreatitis. Classical tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were also tested. We compared the serum level of cytokines with the tumor stage. The diagnostic sensitivity, specificity, positive and negative predictive values and receiver-operating characteristics (ROC) curve for cytokines and classical tumor markers were defined. The cytokines were measured in 48 patients with pancreatic cancer, in 23 patients with chronic pancreatitis and in 40 healthy subjects. HCs were determined using ELISA. CEA and CA 19-9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, IL-3, GM-CSF, M-CSF, CEA and CA 19-9 in the pancreatic cancer patients compared to the control group. The serum levels of M-CSF and tumor markers were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of SCF, M-CSF and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels in the pancreatitis group correlated positively with the tumor markers tested – CEA and CA 19-9. The diagnostic sensitivity of SCF and specificity of M-CSF and tumor markers were the highest. The SCF and M-CSF areas under the ROC curve were greater than the areas for other cytokines. These results suggest the potential usefulness of HCs in pancreatic cancer detection; however, further investigations of early-stage pancreatic cancer patients and confirmation by a prospective study are necessary.


Blood ◽  
1994 ◽  
Vol 83 (10) ◽  
pp. 2893-2898 ◽  
Author(s):  
H Toda ◽  
A Murata ◽  
Y Oka ◽  
K Uda ◽  
N Tanaka ◽  
...  

Abstract The administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with severe active infections has been questioned because activation of neutrophils may cause tissue injury. To identify the effect of GM-CSF administration on severe sepsis, we examined the survival rate and pathologic changes in vital organs using the rat lethal sepsis model. Rats received 20 micrograms of recombinant murine GM-CSF (rmGM-CSF) 3 hours after the onset of peritonitis induced by cecal ligation and puncture. After 48 hours, the survival rate did not improve, and earlier deaths than in the control group were observed. In addition, the inhibition of early leuko-sequestration in the peritoneal cavity was seen in animals treated with GM-CSF. These results suggested that the administration of rmGM-CSF after the onset of sepsis was not beneficial; thus, we concluded that care should be taken in the clinical use of GM-CSF in severe infection.


Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2960-2965 ◽  
Author(s):  
FM Rosenthal ◽  
R Fruh ◽  
R Henschler ◽  
H Veelken ◽  
P Kulmburg ◽  
...  

Abstract Development of cell-based delivery systems that can release therapeutic levels of hematopoietic growth factors into the systemic circulation would facilitate treatment of patients requiring cytokine therapy. In this study, we have investigated the potential of granulocyte- macrophage colony-stimulating factor (GM-CSF)-secreting, irradiated syngeneic murine cells to accelerate hematopoietic recovery after cytotoxic chemotherapy. As a model, CMS-5 fibrosarcoma cells, were transduced with a retroviral vector containing the murine GM-CSF cDNA. Transduced cells secreted 38 ng GM-CSF/10(6) cells in 24 hours. After irradiation, in vitro GM-CSF production initially increased up to fivefold and was measurable for about 2 weeks. One and 2 days after injection of irradiated, GM-CSF-secreting CMS-5 cells (N2/CMVGM- CSF/CMS5 # 6 cells) into mice, GM-CSF serum levels of 405 +/- 58 pg/mL and 183 +/- 36 pg/mL were measured, respectively. Serum levels were comparable with levels detected 3 hours after injection of 100 ng recombinant murine GM-CSF (rmGM-CSF) subcutaneously (90 pg/mL). Injection of N2/CMVGM-CSF/CMS5 # 6 cells in cyclophosphamide-treated mice was as effective in accelerating neutrophil recovery as twice daily subcutaneous injections of rmGM-CSF. These data suggest that irradiated hematopoietic growth factor-secreting cells might offer an alternative to parenteral injections of recombinant cytokines in the treatment of neutropenic patients.


1999 ◽  
Vol 90 (6) ◽  
pp. 1064-1071 ◽  
Author(s):  
Margaret A. Wallenfriedman ◽  
John A. Conrad ◽  
Lance DelaBarre ◽  
Patrick C. Graupman ◽  
Gina Lee ◽  
...  

Object. Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system that directly suppresses immunological defenses in vitro and in vivo. The authors used the peripheral delivery of continuously infused granulocyte—macrophage colony-stimulating factor (GM-CSF) in the presence of irradiated tumor antigens as a tumor-specific stimulant to dendritic cells to initiate an immune response to GBM in rats.Methods. The 9L gliosarcoma tumors were established in the flanks of syngeneic Fischer 344 rats. Osmotic minipumps implanted in the animals' contralateral flanks continuously delivered recombinant GM-CSF (0, 0.1, 1, or 10 ng/day) for 28 days. Irradiated gliosarcoma cells were intermittently injected at the site of the GM-CSF infusion. Animals in the saline control group (0 ng/day GM-CSF) died on Day 59 with average tumor volumes greater than 30,000 mm3. This control group was significantly different from the GM-CSF—treated animals, which all survived with average tumor volumes that peaked on Day 23 and later regressed completely. Tumor growth as well as peak tumor volumes (5833 ± 2284 mm3, 3294 ± 1632 mm3, and 1979 ± 1142 mm3 for 0.1, 1, and 10 ng/day GM-CSF, respectively) in the different treatment groups reflected a significant dose-response relationship with the GM-CSF concentrations. All animals treated with GM-CSF and irradiated cells were resistant to additional challenges of peripheral and intracerebral gliosarcoma, even when they were inoculated 8 months after initial immunotherapy. The colocalization of GM-CSF and inactivated tumor antigens was required to stimulate immunoprotection. To test the efficacy of a peripherally administered immunological therapy on intracerebral brain tumors the authors transplanted 106 gliosarcoma cells into the striatum of treated and control animals. Subcutaneous pumps that released GM-CSF (10 ng/day) and irradiated gliosarcoma cells were placed in the treated animals. The control animals all died within 31 days after intracerebral tumor implantation. In contrast, 40% of the animals receiving GM-CSF—irradiated cell vaccinations survived beyond 300 days. These long-term survivors showed no evidence of gliosarcoma at the injection site on evaluation by magnetic resonance imaging.Conclusions. These results suggest that the continuous localized delivery of subcutaneous GM-CSF in conjunction with inactivated tumor antigens can initiate a systemic response that leads to the regression of distant peripheral and intracerebral tumors. The success of this treatment illustrates the feasibility of tumor-specific peripheral immunological stimulation after tumor resection to prevent the recurrence of malignant brain tumors.


2022 ◽  
Author(s):  
JinTao Guan ◽  
Anran Xi ◽  
DU Jin ◽  
XiaoYue Mou ◽  
Zhenghao Xu

Objective: We performed a meta analysis in order to determine safety of granulocyte macrophage colony stimulating factor (GM CSF) antibodies on COVID 19. Methods: We searched from the Cochrane Library, PubMed, Embase, biorxiv and medrxiv databases beginning in the COVID-19 outbreak on December 1, 2019 until August 29, 2021. The primary outcomes included death, the incidence of invasive mechanical ventilation (IMV), ventilation requirement, and secondary infection. Results: 6 eligible literature involving 1501 COVID 19 patients were recruited, and they were divided into experimental group (n = 736) and control group (n = 765). Using a random effect model, we found that the GM CSF antibodies treatment was associated with a 3.8-26.9% decline of the risk of mortality[odd ratio (OR) = 0.06, 95% confidence interval (CI): -0.11, -0.01, p =0.02], a 5.3-28.7% reduction of incidence of IMV [OR = 0.51, 95% CI: 0.28, 0.95, p =0.03], and a 23.3-50.0% enhancement of ventilation improvement [OR = 11.70, 95% CI: 1.99, 68.68, p=0.006]. There were no statistically significant differences in the association between two groups in second infection. Conclusion: Severe COVID 19 patients may benefit from GM CSF antibodies.


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