China
Africa
Explore chapters and articles related to this topic
Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
The downstream signaling of GM-CSFR is mediated by Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), extracellular signal-regulated kinase (ERK), and the phosphoinositide 3-kinase (PI3K)-Akt pathway. Higher levels of GM-CSF were observed in the early stages (1–3 days), with a steady decrease in the late stages (day 14). GM-CSF may also have unintended consequences. As activated neutrophils play a major role in the microvascular injury that contributes to lung damage, they may contribute to acute respiratory distress syndrome (ARDS) by suppressing neutrophil apoptosis [6].
Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a glycoprotein that binds to a 2-subunit receptor comprising a ligand-specific alpha chain and a common beta chain shared with IL-3 and IL-5. GM-CSF is produced by monocytes, T cells, fibroblasts, endothelial cells, macrophages, and stromal cells, and stimulates the survival of the hematopoietic colony-forming cells of neutrophil, eosinophil, macrophage, megakaryocyte, and erythrocyte linages. The best-known approved GM-CSF product is sargramostim (Leukine™), which is described below.
Immunomodulation in Gene Therapeutics
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Andreas Block, Susan S. Rich, Shu-Hsia Chen, Savio L. C. Woo
Granulocyte macrophage colony stimulating factor (GM-CSF) has a broad range of functions as a growth and survival factor as well as an enhancer of the function of mature blood cells [120–122]. Most of its properties affect progenitors of granulocytes, monocytes, and eosinophils as a growth factor, extending their lifespan and augmenting their functional capability. Neutrophils and macrophages show enhanced antibody-dependent cytotoxicity. In addition, GM-CSF is an important immunopotentiating factor, expanding potent antigen presenting cells [123–125] as well as augmenting antigen presenting abilities of mature macrophages [126,127], and therefore dramatically enhancing the host response to antigen.
Intestinal and systemic inflammation induced by symptomatic and asymptomatic enterotoxigenic E. coli infection and impact on intestinal colonization and ETEC specific immune responses in an experimental human challenge model
Published in Gut Microbes, 2021
Jessica Brubaker, Xueyan Zhang, A. Louis Bourgeois, Clayton Harro, David A Sack, Subhra Chakraborty
A well-recognized feature of infectious diseases is that their clinical course and eventual outcome can vary substantially between infected individuals. In a controlled experimental challenge study, this variability in disease prognosis would largely depend upon the host factors. A better understanding of the determinates of disease outcome could provide unique insights into disease biology as well as potentially revealing new therapeutic targets. Our study showed that higher pre-challenge concentrations of IL-10 and GM-CSF cytokines could be protective in ETEC diarrhea. IL-10 is an anti-inflammatory cytokine produced by dendritic cells, macrophages, and T-helper lymphocytes that downregulates the production of inflammatory mediators.37 It has been shown that IL-10−/− mice are susceptible to continued inflammation as a result of interactions with endogenous gut bacteria at the bowel wall and that in the absence of IL-10 there is an unchecked pro-inflammatory response to luminal organisms.38 GM-CSF is a white blood cell growth factor which stimulates stem cells to produce granulocytes and macrophages, a process crucial for development of the immune system to promote defense against infections.39 Further studies are needed to understand any specific interactions of these cytokines with ETEC and ETEC toxins.
Relationship between granulocyte–macrophage colony-stimulating factor, embryo quality, and pregnancy outcomes in women of different ages in fresh transfer cycles: a retrospective study
Published in Journal of Obstetrics and Gynaecology, 2020
Dapeng Chu, Lei Fu, Wenhui Zhou, Yuan Li
Generally, the concentration of GM-CSF applied in most human studies is 2 ng/mL (Sjöblom et al. 1999; Kim et al. 2001; Sjöblom et al. 2002; Shapiro et al. 2003; Sfontouris et al. 2013; Ziebe et al. 2013), which is likely to be based on data from animal studies. Although the effect of different concentrations of GM-CSF on the development of pre-implantation embryos was examined in animals (Behbnaz et al. 2004; Karagenc et al. 2005; Lee et al. 2013), the same reasoning should not be applied to human embryos. After carefully reviewing the previous studies, the authors did not find any reliable evidence proving that the concentration of 2 ng/mL was similar to the concentration in in vivo animal and human environments. Additionally, some studies indicated that low concentrations of GM-CSF (less than 1 ng/mL) could lead to a significant increase in blastocyst development (Behr et al. 2001; Wang et al. 2002; Behr et al. 2005). Therefore, whether 2 ng/mL is an optimal dosage of GM-CSF for humans is worthy of further investigation. If a lower concentration of GM-CSF can benefit ART clinical outcomes, it will help lighten the economic burden on patients. A previous study explored the effects of GM-CSF at a low concentration (0.2 ng/mL) on patients aged over 35 years (Zhou et al. 2016).
Sevoflurane inhibited inflammatory response induced by TNF-α in human trophoblastic cells through p38MAPK signaling pathway
Published in Journal of Receptors and Signal Transduction, 2020
Li Mo, Shuzhen Hong, Yi Li, Zurong Hu, Baoyi Han, Zaomei Wei, Jie Jia
TNF-α (also known as cachectin) is a cytokine that strongly promotes inflammation, playing pivotal roles in the immune system during the process of differentiation, apoptosis and inflammation [18]. Literature demonstrates that the phosphorylation of PI3K/Akt and the activation of NF-κB pathway induced by paeonol can inhibit TNF-α expressions, as well as TNFα-induced GM-CSF secretion in fibroblast-like synoviocytes [19]. Additionally, TNF-α has been verified in preceding studies to play a pivotal role in inflammatory and autoimmune disorders [20], and the significant TNF-α expressions in maternal perfusate stimulate pro-inflammatory cytokines (IL-6, IL-8, and MCP-1) secretion. Thus, down-regulating the TNF-α expression might be an effective way to alleviate the severity of maternal complications in PE [21]. Monocytes- and macrophages-produced IL-6 is a prototypical cytokine that contributes to host defense by promptly responding to infections and tissue injuries, during which process the activation of immune, hematological, and acute-phase responses are involved. However, the excessive persistence of IL-6 production will in turn motivate the development of chronical inflammatory diseases and cancers [22,23]. Therefore, the proper IL-6 expression for host defense should be strictly controlled. Besides, IL-8 is produced by phagocytes and mesenchymal cells in response of inflammatory stimuli like TNF-α, and is correlated with local neutrophil accumulation [24]. GM-CSF is universally viewed as a pro-inflammation cytokine that takes effects in many autoimmunity/inflammation models [25].