The clinical importance of a cytokine network in the acute phase of sepsis

Abstract

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.

Specific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice

“…Given that IFNAR was required for mortality in IC:LPS (Fig. 1D) and the role of TNF, IL-1, and IL-6 in driving mortality in multiple models of inflammation (32,33), we asked if cytokine blockade would be sufficient to rescue IC:LPS-challenged animals. While TNF blockade extended viability of IC:LPSchallenged animals, blocking TNF, IL-6, IL-1, or IFNAR did not significantly prolong survival (Fig.…”

Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis

“…We observed lower production of IL-1α, IL-1β, IL-6 and TNFα in serum and in peritoneal fluids in GzmA deficient mice. All these cytokines play an important role in sepsis (Chong & Sriskandan, 2011;Linkermann et al, 2012;Matsumoto et al, 2018;Vanden Berghe et al, 2014). In addition, our results employing an inhibitor of extracellular GzmA, Serpinb6b, in vitro and in vivo, strongly suggest that GzmA enhances the inflammatory pathological response in sepsis in the extracellular space.…”

Novel mulberry silkworm cocoon-derived carbon dots and their anti-inflammatory properties

“…The results indicated that the MSC-CDs significantly and dose-dependently decreased the plasma levels of IL-6 and TNF-a, showing a protective phenotype in the pathology. IL-6 and TNF-a are key proinflammatory cytokines of the inflammatory reaction in acute sepsis that act as endogenous pyrogens, up-regulate the activation of secondary effector cells, and are involved in a numerous complex immunological interactions and signalling cascades [38]. Cytokine release is an early event in sepsis pathogenesis and an increase in pro-inflammatory cytokines has been shown to correlate with clinical features such as multiple organ dysfunction and mortality [39].…”