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2020 ; 109
(ä): 154282
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Commentary: Phosphodiesterase 4 inhibitors as potential adjunct treatment
targeting the cytokine storm in COVID-19
#MMPMID32497535
Dalamaga M
; Karampela I
; Mantzoros CS
Metabolism
2020[Aug]; 109
(ä): 154282
PMID32497535
show ga
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-?, 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-?, 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.