Interleukin-6 and Pulmonary Compliance in COVID-19-Related Acute Respiratory Distress Syndrome

This study aims to investigate effects of tocilizumab, a monoclonal antibody to interleukin-6 (IL-6) receptors, on cytokine expression and animal survival in a model of fatal acute respiratory distress syndrome (ARDS) characterized by high mortality rates and increased IL-6 production in the lungs. The expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor (TNF-α) and interferons α (IFN-α) and β (IFN-β) in the lungs was assessed by real-time PCR. Cytokine production was assessed by enzyme immunoassay. Although tocilizumab did not affect the expression of the studied cytokines in the lungs of animals with ARDS, it changed the proﬁles of their release. An acute multifold increase in the levels of IL-6 in the lungs was observed in the ﬁrst two hours after the administration of tocilizumab, followed by a decrease of IL-6 to lower values similar to those observed in intact animals. Tocilizumab did not reduce mortality in treated animals with ARDS compared to those without treatment. Thus, the inhibition of the IL-6 receptor signaling pathway alone does not provide an effective solution to the problem of reducing mortality from ARDS associated with the development of a “cytokine storm”.

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Mesenchymal Stromal Cells Are More Effective Than Their Extracellular Vesicles at Reducing Lung Injury Regardless of Acute Respiratory Distress Syndrome Etiology

Stem Cells International ◽

10.1155/2019/8262849 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 12

Author(s):

Johnatas D. Silva ◽

Ligia L. de Castro ◽

Cassia L. Braga ◽

Gisele P. Oliveira ◽

Stefano A. Trivelin ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Growth Factor ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Extracellular Vesicles ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Interleukin 6 ◽

Distress Syndrome ◽

Therapeutic Effects

Although mesenchymal stromal cells (MSCs) have demonstrated beneficial effects on experimental acute respiratory distress syndrome (ARDS), preconditioning may be required to potentiate their therapeutic effects. Additionally, administration of cell-free products, such as extracellular vesicles (EVs) obtained from MSC-conditioned media, might be as effective as MSCs. In this study, we comparatively evaluated the effects of MSCs, preconditioned or not with serum collected from mice with pulmonary or extrapulmonary ARDS (ARDSp and ARDSexp, respectively), and the EVs derived from these cells on lung inflammation and remodeling in ARDSp and ARDSexp mice. Administration of MSCs (preconditioned or not), but not their EVs, reduced static lung elastance, interstitial edema, and collagen fiber content in both ARDSp and ARDSexp. Although MSCs and EVs reduced alveolar collapse and neutrophil cell counts in lung tissue, therapeutic responses were superior in mice receiving MSCs, regardless of preconditioning. Despite higher total cell, macrophage, and neutrophil counts in bronchoalveolar lavage fluid in ARDSp than ARDSexp, MSCs and EVs (preconditioned or not) led to a similar decrease. In ARDSp, both MSCs and EVs, regardless of preconditioning, reduced levels of tumor necrosis factor- (TNF-) α, interleukin-6, keratinocyte chemoattractant (KC), vascular endothelial growth factor (VEGF), and transforming growth factor- (TGF-) β in lung homogenates. In ARDSexp, TNF-α, interleukin-6, and KC levels were reduced by MSCs and EVs, preconditioned or not; only MSCs reduced VEGF levels, while TGF-β levels were similarly increased in ARDSexp treated either with saline, MSCs, or EVs, regardless of preconditioning. In conclusion, MSCs yielded greater overall improvement in ARDS in comparison to EVs derived from the same number of cells and regardless of the preconditioning status. However, the effects of MSCs and EVs differed according to ARDS etiology.

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Use of Anti-Interleukin-6 Receptor Monoclonal Antibody in Drug-Induced Acute Respiratory Distress Syndrome

Case Reports in Critical Care ◽

10.1155/2020/8832986 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Alessandra Petrillo ◽

Noa Biran ◽

Sean Sadikot

Keyword(s):

Monoclonal Antibody ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Interleukin 6 ◽

Distress Syndrome ◽

Standard Of Care ◽

Drug Induced ◽

Immunological Mechanisms ◽

Interleukin 6 Receptor

Acute respiratory distress syndrome (ARDS) is a disorder that involves the activation of alveolar macrophages triggering the innate immune system. The parenchymal lung injury seen in ARDS is a result of many proinflammatory elevations including interleukin-6. There remains no effective standard of care of ARDS, and current treatments at this time currently do not target the immunological mechanisms or pathways involved. Treatments involving this pathway should be further investigated as targeted treatment. We discuss a case of a patient with multiple myeloma who was hospitalized with drug-induced ARDS who had a rapid response to an anti-interleukin-6 monoclonal antibody.

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Evaluation of von Willebrand factor as a marker for early diagnosis of Acute Respiratory Distress Syndrome in comparison to Interleukin-6

Ain-Shams Journal of Anesthesiology ◽

10.1186/s42077-021-00141-x ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Dalia M. ELfawy ◽

Mohmmed Abd Elkalek ◽

Ehab Hamed ◽

Samer Ibrahem ◽

Doaa M. A. ELzoghby ◽

...

Keyword(s):

At Risk ◽

Acute Respiratory Distress Syndrome ◽

Lung Injury ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Von Willebrand Factor ◽

Interleukin 6 ◽

Distress Syndrome ◽

Von Willebrand ◽

Willebrand Factor

Abstract Background Acute respiratory distress syndrome (ARDS) constitutes a clinical phenotype of severe lung injury associated with many causes. Endothelial activation and injury is a component of ARDS. The release of von Willebrand factor (vWF) indicates direct endothelial cell damage has occurred, and this can be used as a marker of endothelium injury. The aim of the study was to investigate the diagnostic value of vWF antigen as a determinant of early detection of ARDS in comparison to interleukin-6 (IL-6) as a control biomarker. vWF antigen and IL-6 were measured in 60 patients who were at risk of developing ARDS on T0 (at the start of the study), T48 (after 48 h), and T72 (after 72 h). Results Higher vWF Ag levels were seen in patients at risk of developing ARDS with direct cause of lung injury than those with indirect causes. Include groups I and II. There was a highly significant increase between the “at risk of developing ARDS” patients, VWF Ag, and IL-6 levels. The results were recorded at T0 (i.e., at start of the study baseline reading), T48 (after 48 h), and T72 (after 72 h), p 0.001 and p 0.05, respectively. A value of vWF Ag of 447% on the 3rd day of ARDS showed a sensitivity of 94.9% and specificity 56.7% compared to IL-6 at 246 pg/ml with 79.5% sensitivity and 52.4% specificity. As a comparison between VWF and IL6 levels among ARDS patients, they both show statistical correlation together. Conclusion The results of our study point out to VWF as a sensitive and good diagnostic marker for ARDS diagnosis.

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