Phase 2, randomized, double-blind, placebo-controlled multi-center trial of the clinical and biological effects of anti-CD14 treatment in hospitalized patients with COVID-19 pneumonia

Mabrey, F Linzee; Nian, Hui; Yu, Chang; Barnes, Elizabeth M.; Malhotra, Uma; Mikacenic, Carmen; Goldstein, Julia; O’Mahony, D. Shane; Garcia-Diaz, Julia; Voelker, Kirk; Morrell, Eric D.; Self, Wesley H.; Becker, Patrice M.; Martin, Thomas R.; Wurfel, Mark M.

doi:10.1016/j.ebiom.2023.104667

Cited by 7 publications

(3 citation statements)

References 46 publications

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“…demonstrating that CD14 blockade did not improve the time-to-resolution of illness in hypoxemic patients with COVID-19. 30 In summary, the current study supports the notion that IVC stenosis results in increased plasma G-CSF levels, neutrophilia, and neutrophil hyperactivation. Moreover, neutrophils isolated post-IVC stenosis exhibit overexpression of CD14.…”

Section: Relationship Disclosuressupporting

confidence: 85%

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CD14 Blockade Does Not Improve Outcomes of Deep Vein Thrombosis Following Inferior Vena Cava Stenosis in Mice

Pandey,

Kaur,

Chandaluri

et al. 2024

Preprint

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Background: Neutrophil-mediated persistent inflammation and neutrophil extracellular trap formation (NETosis) promote deep vein thrombosis (DVT). CD14, a co-receptor for toll-like receptor 4 (TLR4), is actively synthesized by neutrophils, and the CD14/TLR4 signaling pathway has been implicated in proinflammatory cytokine overproduction and several aspects of thromboinflammation. The role of CD14 in the pathogenesis of DVT remains unclear. Objective: To determine whether CD14 blockade improves DVT outcomes. Methods: Bulk RNA sequencing and proteomic analyses were performed using isolated neutrophils following inferior vena cava (IVC) stenosis in mice. DVT outcomes (IVC thrombus weight and length, thrombosis incidence, neutrophil recruitment, and NETosis) were evaluated following IVC stenosis in mice treated with a specific anti-CD14 antibody, 4C1, or control antibody. Results: Mice with IVC stenosis exhibited increased plasma levels of granulocyte colony-stimulating factor (G-CSF) along with a higher neutrophil-to-lymphocyte ratio and increased plasma levels of cell-free DNA, elastase, and myeloperoxidase. Quantitative measurement of total neutrophil mRNA and protein expression revealed distinct profiles in mice with IVC stenosis compared to mice with sham surgery. Neutrophils of mice with IVC stenosis exhibited increased inflammatory transcriptional and proteomic responses, along with increased expression of CD14. Treatment with a specific anti-CD14 antibody, 4C1, did not result in any significant changes in the IVC thrombus weight, thrombosis incidence, or neutrophil recruitment to the thrombus. Conclusion: The results of the current study are important for understanding the role of CD14 in the regulation of DVT and suggest that CD14 lacks an essential role in the pathogenesis of DVT following IVC stenosis.

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Section: Relationship Disclosuressupporting

confidence: 85%

“…Nevertheless, we speculate that such a scenario is unlikely because of a recent phase 2 trial demonstrating that CD14 blockade did not improve the time-to-resolution of illness in hypoxemic patients with COVID-19. 30…”

Section: Resultsmentioning

confidence: 99%

CD14 Blockade Does Not Improve Outcomes of Deep Vein Thrombosis Following Inferior Vena Cava Stenosis in Mice

Pandey,

Kaur,

Chandaluri

et al. 2024

Preprint

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“…In fact, IC14, a chimeric monoclonal antibody, is a potential anti-CD14 therapeutic agent that has been investigated in COVID-19 patients. 17 Thus, IC14 may also be useful for treatment of gout by blocking the interactions of CD14, DAMPs and MSU, thereby attenuating the NLRP3/IL-1β pathway.…”

Section: Crystal Arthropathies Crystal Arthropathies Crystal Arthropa...mentioning

confidence: 99%

Spontaneous resolution of acute gout: mechanisms and therapeutic targets

Shi,

Luo,

Ding

et al. 2023

RMD Open

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Gout is a common inflammatory arthritis that has been increasing in both prevalence and incidence. Consequently, management of refractory and chronic gout has been gaining attention. Onset of gout is related to the deposition of monosodium urate crystals under hyperuricaemia. Interestingly, acute gout attacks often resolve spontaneously within 7–10 days, and many studies have confirmed the notion that gout flares can be self-relieved. However, the underlying mechanism for spontaneous remission of gout requires further elucidation. In this article, we summarise the roles and mechanisms related to spontaneous remission of gout, which are essential for understanding its pathogenesis and developing potential targeted therapies.

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