ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025
Selective phosphodiesterase 4 inhibitor roflumilast reduces inflammation and lung injury in models of betacoronavirus infection in mice.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Annexin A1 as a key modulator of lung inflammation during coronavirus infections.Clinical science (London, England : 1979) · 2025Article
- Molecular Properties of Phosphodiesterase 4 and Its Inhibition by Roflumilast and Cilomilast.Molecules (Basel, Switzerland) · 2025Review
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Authors and funding
16 authors.
Funding
Abstract
objectiveWe aimed to understand the potential therapeutic and anti-inflammatory effects of the phosphodiesterase-4 (PDE4) inhibitor roflumilast in models of pulmonary infection caused by betacoronaviruses.
methodsMice were infected intranasally with murine hepatitis virus (MHV-3) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Roflumilast was given to MHV-3-infected mice therapeutically at doses of 1 mg/kg or 10 mg/kg, or prophylactically at 10 mg/kg. In SARS-CoV-2-infected mice, roflumilast was given therapeutically at a dose of 10 mg/kg. Lung histopathology, chemokines (CXCL-1 and CCL2), cytokines (IL-1β, IL-6, TNF, IFN-γ, IL-10 and TGFβ), neutrophil immunohistochemical staining (Ly6G
resultsTherapeutic treatment with roflumilast at 10 mg/kg reduced lung injury in SARS-CoV-2 or MHV-3-infected mice without compromising viral clearance. In MHV-3-infected mice, reduced lung injury was associated with decreased chemokines levels, prevention of neutrophil aggregates and reduced macrophage accumulation in the lung tissue. However, the prophylactic treatment strategy with roflumilast increased lung injury in MHV-3-infected mice.
conclusionOur findings indicate that therapeutic treatment with roflumilast reduced lung injury in MHV-3 and SARS-CoV-2 lung infections. Given the protection induced by roflumilast in inflammation, PDE4 targeting could be a promising therapeutic avenue worth exploring following severe viral infections of the lung.
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Registered trials
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