scholarly journals Granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies treatment for COVID-19 patients: a meta-analysis

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.

2021 ◽  
Vol 12 ◽  
pp. 204062232110396
Author(s):  
Jin-Tao Guan ◽  
Wei-Jie Wang ◽  
Du Jin ◽  
Xiao-Yue Mou ◽  
Shan-Shan Lei ◽  
...  

Objective: This meta-analysis aims to assess the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies on COVID-19. Methods: Relevant literatures about GM-CSF antibody treatment in COVID-19 patients were searched from the PubMed, Cochrane Library, Embase, Google scholar, and Baiduscholar databases from the COVID-19 outbreak in December 2019 until 1 January 2021. The primary outcomes included the death, intensive care unit (ICU) admission risk, ventilation requirement, and secondary infection. Results: A total of 12 eligible literature involving 8979 COVID-19 patients were recruited, and they were divided into experimental group ( n = 2673) and control group ( n = 6306). Using a random-effect model, it is found that the GM-CSF antibody treatment was associated with a 23% decline of the risk of death [odd’s ratio (OR): 0.34, 95% confidence interval (CI): 0.21–0.56, p < 0.0001] and a 20% enhancement of ventilation (OR: 1.47, 95% CI: 1.19, 1.80, p = 0.0002). GM-CSF antibody treatment did not have a significant correlation to secondary infection and increased risk of ICU admission in COVID-19 patients, which may be attributed to the older age and the length of stay. Conclusions: Severe COVID-19 patients can benefit from GM-CSF antibodies.


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.


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.


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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jani Lappalainen ◽  
Nicolas Yeung ◽  
Su D. Nguyen ◽  
Matti Jauhiainen ◽  
Petri T. Kovanen ◽  
...  

AbstractIn atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte–macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MØ and GM-MØ, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MØ, the M-MØ expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MØ foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MØ strongly suppressed the high baseline expression of CCL2, whereas in GM-MØ the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.


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