JAK–STAT Targeting Offers Novel Therapeutic Opportunities in Sepsis

Sepsis is a life-threatening condition caused by exaggerated host responses to infections taking place in two phases: (i) a systemic (hyper)inflammatory response syndrome (SIRS), participating in multiple organ failure (MOF), a major complication of septic shock, followed by (ii) a compensatory anti-inflammatory response syndrome (CARS), leading to sepsis-induced immunosuppression and resulting in late infections and long-term mortality. The Janus kinase-signal transducer and activator of transcription (JAK-STAT)-dependent signaling pathway is involved in both manifestations, hence playing a key role during sepsis. It is also involved in emergency myelopoiesis, which participates in host defense. The aim of this review is to highlight and refine the recent implications of this signaling pathway in sepsis and illustrate why its central position makes it a potential biomarker and therapeutic target.