IL-33 Depletion in COVID-19 Lungs

Gaurav, Rohit; Anderson, Daniel R.; Radio, Stanley J.; Bailey, Kristina L.; England, Bryant R.; Mikuls, Ted R.; Thiele, Geoffrey M.; Strah, Heather; Romberger, Debra J.; Wyatt, Todd A.; Dickinson, John D.; Duryee, Michael J.; Katafiasz, Dawn M.; Nelson, Amy; Poole, Jill

doi:10.1016/j.chest.2021.06.058

Cited by 17 publications

(22 citation statements)

References 11 publications

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“…Upon SARS-CoV-2 infection, IL-17 levels, along with other Th17 related proinflammatory cytokines, such as IL-1, IL-6, IL-15, TNF, and IFN-γ, are increased, which has a positive correlation with disease severity ( 101 , 102 , 208 ). Previous reports indicating the elevation of IL-17 levels in patients with SARS-CoV or MERS ( 209 , 210 ) as well as elevated IL-17 levels in SARS-CoV-2-induced cytokine storm ( 33 ), ALI ( 102 ), ARDS ( 37 ), viral load have been reported ( 77 , 211 ). A Janus kinase 2 inhibitor, Fedratinib, has been used to decrease IL-17 expression by inhibiting Th17 cells in murine models ( 212 ).…”

Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 86%

“…IL-33 is an alarming and crucial immune modulator released by endothelial and epithelial cells, activated fibroblasts, fibroblast-like cells, and myofibroblasts to maintain the tissue and immune homeostasis and inflammation through IL-33/ST2 signaling ( 211 , 213 ). IL-33 plays important roles during allergic, fibrotic, infectious, and chronic inflammatory diseases by activating the different immune subgroups, such as Th1, Th2, T Reg , CD8 + T cells, mast cells, group 2 innate lymphoid cells (ILC2s), granulocytes, macrophages, DCs, NK cells, iNKT cells, and B cells ( 209 , 210 , 213 , 214 ).…”

Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 99%

“…In COVID-19 patients, increased IL-33 serum levels were associated with poor outcomes ( 209 , 215 – 217 ). IL-33 activation could induce a type-2 immune response by inducing ILC2s ( 217 ).…”

Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 99%

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The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Hsu

Peng

et al. 2022

Front. Immunol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence in 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is caused by uncontrolled inflammation, aberrant immune response, cytokine storm, and an imbalanced hyperactive immune system. The cytokine storm further results in multiple organ failure and lung immunopathology. Therefore, any potential treatments should focus on the direct elimination of viral particles, prevention strategies, and mitigation of the imbalanced (hyperactive) immune system. This review focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines. In addition to the review focus, we discuss potential immunotherapeutic approaches based on relevant pathophysiological features, the systemic immune response against SARS-CoV-2, and data from recent clinical trials and experiments on the COVID-19-associated cytokine storm. Prompt use of these cytokines as diagnostic markers and aggressive prevention and management of the cytokine storm can help determine COVID-19-associated morbidity and mortality. The prophylaxis and rapid management of the cytokine storm appear to significantly improve disease outcomes. For these reasons, this study aims to provide advanced information to facilitate innovative strategies to survive in the COVID-19 pandemic.

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Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 86%

Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Hsu

Peng

et al. 2022

Front. Immunol.

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“…Lung tissues were stained and analyzed for CIT- and MAA-modified antigens that included vimentin. Vimentin is an extracellular matrix protein that is increased in inflammatory lung diseases such as RA-ILD [ 34 , 41 , 42 ] and can be targeted by post-translational protein modifications, as demonstrated by robust co-localization with MAA in RA-ILD lung tissues [ 41 ]. By confocal microscopy, CIT- and MAA-modified proteins as well as vimentin were significantly increased in WT-ODE and DR4-ODE as compared to respective saline controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Beyond these inflammatory mediators, our studies have demonstrated that lung IL-33 levels are increased following airborne biohazard exposures, particularly in DR4 mice. As an alarmin that forms in response to damage or stress signals, IL-33 is increased in several inflammatory and fibrotic lung diseases that include COPD, idiopathic pulmonary fibrosis (IPF), post-COVID lung fibrosis, and RA-ILD [ 34 , 42 ]. Given that clinical studies targeting the systemic IL-33 signaling pathway are currently underway in the treatment of COPD (clinicaltrials.gov; NCT04701983; NCT03615040), investigating the role of IL-33 in HLA-DRB1 + RA and lung diseases resulting from airborne exposures may be warranted.…”

Section: Discussionmentioning

confidence: 99%

Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice

et al. 2022

Self Cite

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Immunogenetic as well as environmental and occupational exposures have been linked to the development of rheumatoid arthritis (RA), RA-associated lung disease, and other primary lung disorders. Importantly, various inhalants can trigger post-translational protein modifications, resulting in lung autoantigen expression capable of stimulating pro-inflammatory and/or pro-fibrotic immune responses. To further elucidate gene-environment interactions contributing to pathologic lung inflammation, we exploited an established model of organic dust extract (ODE) exposure with and without collagen-induced arthritis (CIA) in C57BL/6 wild type (WT) versus HLA-DR4 transgenic mice. ODE-induced airway infiltration driven by neutrophils was significantly increased in DR4 versus WT mice, with corresponding increases in bronchoalveolar lavage fluid (BALF) levels of TNF-⍺, IL-6, and IL-33. Lung histopathology demonstrated increased number of ectopic lymphoid aggregates comprised of T and B cells following ODE exposure in DR4 mice. ODE also induced citrullination, malondialdehyde acetaldehyde (MAA) modification, and vimentin expression that co-localized with MAA and was enhanced in DR4 mice. Serum and BALF anti-MAA antibodies were strikingly increased in ODE-treated DR4 mice. Coupling ODE exposure with Type II collagen immunization (CIA) resulted in similarly augmented pro-inflammatory lung profiles in DR4 mice (relative to WT mice) that was accompanied by a profound increase in infiltrating lung CD4+ and CD8+ T cells as well as CD19+CD11b+ autoimmune B cells. Neither modeling strategy induced significant arthritis. These findings support a model in which environmental insults trigger enhanced post-translational protein modification and lung inflammation sharing immunopathological features with RA-associated lung disease in the selected immunogenetic background of HLA-DR4 mice.

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The roles of critical pro‐inflammatory cytokines in the drive of cytokine storm during SARS‐CoV‐2 infection

Qudus

Tian

Sirajuddin

et al. 2023

Journal of Medical Virology

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In patients with severe COVID-19, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and even mortality can result from cytokine storm, which is a hyperinflammatory medical condition caused by the excessive and uncontrolled release of pro-inflammatory cytokines. High levels of numerous crucial pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-α, interferon (IFN)-γ, IFN-induced protein 10 kDa, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1, and IL-10 and so on, have been found in severe COVID-19. They participate in cascade amplification pathways of pro-inflammatory responses through complex inflammatory networks. Here, we review the involvements of these critical inflammatory cytokines in SARS-CoV-2 infection and discuss their potential roles in triggering or regulating cytokine storm, which can help to understand the pathogenesis of severe COVID-19. So far, there is rarely effective therapeutic strategy for patients with cytokine storm besides using glucocorticoids, which is proved to result in fatal side effects. Clarifying the roles of key involved cytokines in the complex inflammatory network of cytokine storm will help to develop an ideal therapeutic intervention, such as neutralizing antibody of certain cytokine or inhibitor of some inflammatory signal pathways.

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IL-33 Depletion in COVID-19 Lungs

Cited by 17 publications

References 11 publications

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice

The roles of critical pro‐inflammatory cytokines in the drive of cytokine storm during SARS‐CoV‐2 infection

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