Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies.

Autor:	Bonaventura A; Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, United States.; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.; Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States., Vecchié A; Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, United States.; Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States., Wang TS; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, United States., Lee E; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, United States., Cremer PC; Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, United States., Carey B; Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Rajendram P; Respiratory Institute, Cleveland Clinic, Clevaland, OH, United States., Hudock KM; Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati, Cincinnati, OH, United States.; Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Korbee L; Academic Regulatory & Monitoring Services, LLC, Cincinnati, OH, United States., Van Tassell BW; Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, United States., Dagna L; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy., Abbate A; Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, United States.; Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Jul 03; Vol. 11, pp. 1625. Date of Electronic Publication: 2020 Jul 03 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.01625
Abstrakt:	COVID-19 is a clinical syndrome ranging from mild symptoms to severe pneumonia that often leads to respiratory failure, need for mechanical ventilation, and death. Most of the lung damage is driven by a surge in inflammatory cytokines [interleukin-6, interferon-γ, and granulocyte-monocyte stimulating factor (GM-CSF)]. Blunting this hyperinflammation with immunomodulation may lead to clinical improvement. GM-CSF is produced by many cells, including macrophages and T-cells. GM-CSF-derived signals are involved in differentiation of macrophages, including alveolar macrophages (AMs). In animal models of respiratory infections, the intranasal administration of GM-CSF increased the proliferation of AMs and improved outcomes. Increased levels of GM-CSF have been recently described in patients with COVID-19 compared to healthy controls. While GM-CSF might be beneficial in some circumstances as an appropriate response, in this case the inflammatory response is maladaptive by virtue of being later and disproportionate. The inhibition of GM-CSF signaling may be beneficial in improving the hyperinflammation-related lung damage in the most severe cases of COVID-19. This blockade can be achieved through antagonism of the GM-CSF receptor or the direct binding of circulating GM-CSF. Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. Prospective, randomized, placebo-controlled trials are ongoing. Anti-GM-CSF monoclonal antibodies, TJ003234 and gimsilumab, will be tested in clinical trials in patients with COVID-19, while lenzilumab received FDA approval for compassionate use. These trials will help inform whether blunting the inflammatory signaling provided by the GM-CSF axis in COVID-19 is beneficial. (Copyright © 2020 Bonaventura, Vecchié, Wang, Lee, Cremer, Carey, Rajendram, Hudock, Korbee, Van Tassell, Dagna and Abbate.)
Databáze:	MEDLINE
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