6.3 Roflumilast and inflammatory sepsis
Previous findings stated that Janus kinase (JAK)/Signal transducer and
activator of transcription-3 (STAT-3) was a key cellular signal
transduction pathway proved to mediate the expression of many
inflammatory cytokines produced during sepsis (Cai et al., 2015). That
pathway resembles a positive feed-back signal for exacerbating the
inflammatory response, resulting in uncontrolled systemic inflammation
(Chang et al., 2019).
Moreover, during sepsis, there is also an inflammation-induced
activation of coagulation as a result of the concomitant impairment of
endothelial function, anticoagulant and fibrinolytic systems, indicating
that systemic inflammation will be the main pathological reaction of
sepsis and the major cause for associated multiple organ failure
(Schouten et al., 2008). Therefore, reducing inflammation could be the
key for treating sepsis.
Regarding the role of roflumilast in suppressing the mRNA expression of
JAK/STAT-3 signaling pathway with subsequent inhibition of inflammatory
cytokine release (e.g. IL-6 and TNF-α) in the lung tissue of septic mice
model (Chang et al., 2019), there is a proof of its protecting effect
against sepsis through the above-referred anti-inflammatory and
anti-thrombotic activities.