ArticleMetabolism: clinical and experimental2020
Commentary: Phosphodiesterase 4 inhibitors as potential adjunct treatment targeting the cytokine storm in COVID-19.
Article in Metabolism: clinical and experimental, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Topical ronomilast alone or combined with clobetasol ameliorates imiquimod-induced psoriasis in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- PDE4D-CXCL13 axis in gland epithelial cells promotes B cell infiltration in primary Sjögren's syndrome.Acta pharmacologica Sinica · 2026Article
- Selective phosphodiesterase 4 inhibitor roflumilast reduces inflammation and lung injury in models of betacoronavirus infection in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Integrin αProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Modulation of Human Dendritic Cell Functions by Phosphodiesterase-4 Inhibitors: Potential Relevance for the Treatment of Respiratory Diseases.Pharmaceutics · 2023Review
- Dermatology Publications on COVID-19 during the First Pandemic Year: Creativity or Opportunism?Life (Basel, Switzerland) · 2023Article
- Perspectives in vaccines, immune response, therapeutic interventions and COVID-19.Metabolism open · 2023Article
- TheMetabolism open · 2022Review
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- A chromatin remodeling checkpoint of diet-induced macrophage activation in adipose tissue.Metabolism open · 2022Article
- Of mice and men: Considerations on adipose tissue physiology in animal models of obesity and human studies.Metabolism open · 2022Article
- Phase separation may drive mitochondrial nucleoid compartmentation.Metabolism open · 2022Article
- Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges.Metabolism open · 2022Article
- Identification of novel off targets of baricitinib and tofacitinib by machine learning with a focus on thrombosis and viral infection.Scientific reports · 2022Article
- Apremilast Improves Endothelial Glycocalyx Integrity, Vascular and Left Ventricular Myocardial Function in Psoriasis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Antirheumatic Drugs against COVID-19 from the Perspective of Rheumatologists.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Gut probiotic Lactobacillus rhamnosus attenuates PDE4B-mediated interleukin-6 induced by SARS-CoV-2 membrane glycoprotein.The Journal of nutritional biochemistry · 2021Article
- Review
- Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives.Current obesity reports · 2021Review
- Host metabolic reprogramming in response to SARS-CoV-2 infection: A systems biology approach.Microbial pathogenesis · 2021Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The most severe presentation of COVID-19 is characterized by a hyperinflammatory state attributed to the massive pro-inflammatory cytokine release, called "cytokine storm". Several specific anti-inflammatory/immunosuppressive agents are being evaluated by ongoing clinical trials; however, there is currently insufficient evidence for their efficacy and safety in COVID-19 treatment. Given the role of phosphodiesterase 4 (PDE) 4 and cyclic adenosine monophosphate in the inflammatory response, we hypothesize that selective PDE4 inhibition may attenuate the cytokine storm in COVID-19, through the upstream inhibition of pro-inflammatory molecules, particularly TNF-α, and the regulation of the pro-inflammatory/anti-inflammatory balance. Conversely, other anti-cytokine agents lead to the downstream inhibition of specific targets, such as IL-1, IL-6 or TNF-α, and may not be efficient in blocking the cytokine storm, once it has been triggered. Due to their mechanism of action targeting an early stage of the inflammatory response and ameliorating lung inflammation, we believe that selective PDE4 inhibitors may represent a promising treatment option for the early phase of COVID-19 pneumonia before the cytokine storm and severe multiorgan dysfunction take place. Furthermore, PDE4 inhibitors present several advantages including an excellent safety profile; the oral route of administration; the convenient dosing; and beneficial metabolic properties. Interestingly, obesity and diabetes mellitus type 2 have been reported to be risk factors for the severity of COVID-19. Therefore, randomized clinical trials of PDE4 inhibitors are necessary to explore their potential therapeutic effect as an adjunct to supportive measures and other therapeutic regiments.
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