The Roles of Neutrophils in Cytokine Storms

A cytokine storm is an abnormal discharge of soluble mediators following an inappropriate inflammatory response that leads to immunopathological events. Cytokine storms can occur after severe infections as well as in non-infectious situations where inflammatory cytokine responses are initiated, then exaggerated, but fail to return to homeostasis. Neutrophils, macrophages, mast cells, and natural killer cells are among the innate leukocytes that contribute to the pathogenesis of cytokine storms. Neutrophils participate as mediators of inflammation and have roles in promoting homeostatic conditions following pathological inflammation. This review highlights the advances in understanding the mechanisms governing neutrophilic inflammation against viral and bacterial pathogens, in cancers, and in autoimmune diseases, and how neutrophils could influence the development of cytokine storm syndromes. Evidence for the destructive potential of neutrophils in their capacity to contribute to the onset of cytokine storm syndromes is presented across a multitude of clinical scenarios. Further, a variety of potential therapeutic strategies that target neutrophils are discussed in the context of suppressing multiple inflammatory conditions.

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Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?

10.20944/preprints202006.0183.v1 ◽

2020 ◽

Author(s):

Ligong Lu ◽

Hui Zhang ◽

Meixiao Zhan ◽

Jun Jiang ◽

Hua Yin ◽

...

Keyword(s):

Clinical Trials ◽

Severe Acute Respiratory Syndrome ◽

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Inflammatory Mediator ◽

Therapeutic Strategies ◽

Cytokine Storm ◽

Critical Factors ◽

Patient Death ◽

Three Stages

Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.

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Faculty Opinions recommendation of Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1013028.190516 ◽

2003 ◽

Author(s):

Jeffrey Cohen

Keyword(s):

Human Cytomegalovirus ◽

Inflammatory Cytokine ◽

Toll Like Receptor ◽

Cytokine Responses ◽

Toll Like Receptor 2

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Is Immune Response Relevant in Interstitial Lung Disease?

Current Immunology Reviews ◽

10.2174/1573395516999200914143054 ◽

2020 ◽

Vol 16 (1) ◽

pp. 18-27

Author(s):

Manzoor M. Khan

Keyword(s):

Immune Response ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Lung Fibrosis ◽

Lymphocytic Infiltration ◽

Therapeutic Strategies ◽

Mediators Of Inflammation ◽

Acquired Immune Responses ◽

Novel Therapeutic Strategies

Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.

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Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses

Journal of Proteome Research ◽

10.1021/acs.jproteome.1c00052 ◽

2021 ◽

Author(s):

Nathan G. Lawler ◽

Nicola Gray ◽

Torben Kimhofer ◽

Berin Boughton ◽

Melvin Gay ◽

...

Keyword(s):

Inflammatory Cytokine ◽

Cytokine Responses ◽

Kynurenine Metabolism

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Pro-inflammatory cytokine responses in human gingival epithelial cells after stimulation with cell wall extract of Aggregatibacter actinomycetemcomitans subtypes

Anaerobe ◽

10.1016/j.anaerobe.2017.08.001 ◽

2017 ◽

Vol 48 ◽

pp. 103-109 ◽

Cited By ~ 5

Author(s):

Nuntiya Pahumunto ◽

Pareena Chotjumlong ◽

Anupong Makeudom ◽

Suttichai Krisanaprakornkit ◽

Gunnar Dahlen ◽

...

Keyword(s):

Cell Wall ◽

Epithelial Cells ◽

Inflammatory Cytokine ◽

Aggregatibacter Actinomycetemcomitans ◽

Cytokine Responses ◽

Gingival Epithelial Cells ◽

Cell Wall Extract ◽

Human Gingival Epithelial Cells

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Cell Death in Coronavirus Infections: Uncovering Its Role during COVID-19

Cells ◽

10.3390/cells10071585 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1585

Author(s):

Annamaria Paolini ◽

Rebecca Borella ◽

Sara De Biasi ◽

Anita Neroni ◽

Marco Mattioli ◽

...

Keyword(s):

Cell Death ◽

Immune Cells ◽

Viral Infections ◽

Virus Entry ◽

Therapeutic Strategies ◽

The Other ◽

Cytokine Storm ◽

Cytokines And Chemokines ◽

Cell Death Mechanisms ◽

The One

Cell death mechanisms are crucial to maintain an appropriate environment for the functionality of healthy cells. However, during viral infections, dysregulation of these processes can be present and can participate in the pathogenetic mechanisms of the disease. In this review, we describe some features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some immunopathogenic mechanisms characterizing the present coronavirus disease (COVID-19). Lymphopenia and monocytopenia are important contributors to COVID-19 immunopathogenesis. The fine mechanisms underlying these phenomena are still unknown, and several hypotheses have been raised, some of which assign a role to cell death as far as the reduction of specific types of immune cells is concerned. Thus, we discuss three major pathways such as apoptosis, necroptosis, and pyroptosis, and suggest that all of them likely occur simultaneously in COVID-19 patients. We describe that SARS-CoV-2 can have both a direct and an indirect role in inducing cell death. Indeed, on the one hand, cell death can be caused by the virus entry into cells, on the other, the excessive concentration of cytokines and chemokines, a process that is known as a COVID-19-related cytokine storm, exerts deleterious effects on circulating immune cells. However, the overall knowledge of these mechanisms is still scarce and further studies are needed to delineate new therapeutic strategies.

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