Τίτλος:
Commentary: Phosphodiesterase 4 inhibitors as potential adjunct treatment targeting the cytokine storm in COVID-19
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2020 Elsevier Inc.
Συγγραφείς:
Dalamaga, M.
Karampela, I.
Mantzoros, C.S.
Περιοδικό:
Metabolism: Clinical and Experimental
Λέξεις-κλειδιά:
4 (3 chlorophenyl) 1,7 diethylpyrido[2,3 d]pyrimidin 2(1h) one; 6 [3 (dimethylcarbamoyl)phenylsulfonyl] 4 (3 methoxyanilino) 8 methyl 3 quinolinecarboxamide; apremilast; cilomilast; crisaborole; cyclic AMP; elbimilast; gamma interferon; gs 5759; interleukin 1; interleukin 10; interleukin 12; interleukin 13; interleukin 17; interleukin 2; interleukin 22; interleukin 4; interleukin 6; oglemilast; phosphodiesterase IV; phosphodiesterase IV inhibitor; revamilast; tanimilast; tetomilast; tumor necrosis factor; unclassified drug; cyclic AMP; interleukin 17; phosphodiesterase IV inhibitor, antiinflammatory activity; coronavirus disease 2019; cytokine release; cytokine storm; disease severity; drug efficacy; drug safety; enzyme inhibition; human; multiple organ failure; non insulin dependent diabetes mellitus; nonhuman; Note; obesity; pneumonia; priority journal; risk factor; Severe acute respiratory syndrome coronavirus 2; treatment outcome; Betacoronavirus; complication; Coronavirus infection; cytokine release syndrome; immunology; metabolism; pandemic; virus pneumonia, Betacoronavirus; Coronavirus Infections; Cyclic AMP; Cytokine Release Syndrome; Humans; Interleukin-17; Obesity; Pandemics; Phosphodiesterase 4 Inhibitors; Pneumonia, Viral
DOI:
10.1016/j.metabol.2020.154282
