transforming-growth-factor-beta and Cytokine-Release-Syndrome

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The central pathogenesis is an explosive cytokine storm characterized by a significant increase in proinflammatory cytokines, including IL-1β, IL-6, IL-18, IFN-γ, and TNF-α. Meanwhile, negative regulatory factors, such as IL-10 and TGF-β, are also related to the production of HLH. Exploring the specific mechanism of cytokine storms could provide ideas regarding targeted therapy, which could be helpful for early treatment to reduce the mortality of HLH. Although some research has focused on the advantages of targeted therapies, there is still a lack of a comprehensive discourse. This article attempts to summarize the mechanisms of action of various cytokines and provide a therapeutic overview of the current targeted therapies for HLH.

Topics: Cytokine Release Syndrome; Cytokines; Humans; Interleukin-10; Interleukin-18; Interleukin-6; Lymphohistiocytosis, Hemophagocytic; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in severe fever with thrombocytopenia syndrome (SFTS) and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19 patients and also investigated the role of interleukin-10 (IL-10) in vitro studies: lipopolysaccharide-induced THP-1-derived macrophages, SFTSV infection of THP-1 cells, and SARS-CoV-2 infection of THP-1 cells. In this study, we found that levels of both IL-10 and IL-6 were significantly elevated, the level of transforming growth factor-β (TGF-β) was significantly decreased and IL-10 was elevated earlier than IL-6 in severe and critical COVID-19 and fatal SFTS patients, and inhibition of IL-10 signaling decreased the production of IL-6 and elevated that of TGF-β. Therefore, the hyperproduction of IL-10 and IL-6 and the low production of TGF-β have been linked to cytokine storm-induced mortality in fatal SFTS and severe and critically ill COVID-19 patients and that IL-10 can play an important role in the host immune response to severe and critical SARS-CoV-2 and fatal SFTSV infection.

Topics: COVID-19; Cytokine Release Syndrome; Cytokines; Humans; Interleukin-10; Interleukin-6; SARS-CoV-2; Severe Fever with Thrombocytopenia Syndrome; Transforming Growth Factor beta

Pudilan (PDL), a four-herb prescription with the traditional function of heat-clearing and detoxifying, has been clinically used as an anti-SARS-CoV-2 infectory agent in China. PDL might also have therapeutic potentials for COVID-19 while the underlying mechanisms remain to be clarified.. We used network pharmacology analysis and selected 68 co-targeted genes/proteins as targets of both PDL and COVID-19. These co-targeted genes/proteins were predicted by SwissDock Server for their high-precision docking simulation, and analyzed by STRING for proteins to protein interaction (PPI), pathway and GO (gene ontology) enrichment. The therapeutic effect for PDL treatment on COVID-19 was validated by the TCMATCOV (TCM Anti COVID-19) platform.. PDL might prevent the entrance of SARS-CoV-2 entry into cells by blocking the angiotensin-converting enzyme 2 (ACE2). It might inhibit the cytokine storm by affecting C-reactive protein (CRP), interferon-γ (IFN-γ), interleukin- 6 (IL-6), interleukin- 10 (IL-10), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), C-C motif chemokine ligand 5 (CCL5), transforming growth factor-β1 (TGFβ1), and other proteins. PDL might moderate the immune system to shorten the course of the disease, delay disease progression, and reduce the mortality rate.. PDL might have a therapeutic effect on COVID-19 through three aspects, including the moderate immune system, anti-inflammation, and anti-virus entry into cells.

Topics: Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Drugs, Chinese Herbal; Humans; Immunologic Factors; Interferon-gamma; Interleukins; Molecular Docking Simulation; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Interaction Maps; SARS-CoV-2; Transforming Growth Factor beta; Virus Internalization

The outbreak of the highly contagious and deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), has posed a serious threat to public health across the globe, calling for the development of effective diagnostic markers and therapeutics. Here, we report a highly reliable severity diagnostic biomarker, acetylated 676th lysine transforming growth factor-beta-induced protein (TGFBIp K676Ac). TGFBIp K676Ac was consistently elevated in the blood of patients with SARS-CoV-2 pneumonia (

Topics: Acetylation; Antibodies, Neutralizing; Betacoronavirus; Biomarkers; Case-Control Studies; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Extracellular Matrix Proteins; Gene Expression; Humans; Intensive Care Units; Leukocyte Count; Leukocytes, Mononuclear; Lung; Lysine; NF-kappa B; Pandemics; Pneumonia, Viral; Primary Cell Culture; Prognosis; Protein Processing, Post-Translational; Respiratory Insufficiency; SARS-CoV-2; Severity of Illness Index; Transforming Growth Factor beta