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.