Sepsis was induced using cecal ligation and puncture (CLP) in wild-type (WT) mice, IL-18 knockout (KO) mice, and IL-18 KO mice pretreated with recombinant IL-18.
IL18 promoter polymorphism, especially at -607, may increase IL18 production in some patients and might be useful in predicting the outcome of patients with sepsis in the ICU.
According to our results the IL-18 is a biomarker better differentiating sepsis and septic shock status than PCT, CRP and WBC but with no prognostic impact.
Based on the present data, monitoring levels of serum chemokines and IL-18 protein as markers of sepsis might be misleading since despite their non-detection in serum, they were highly up-regulated in the lung tissue compartment.
Caspase-12 is generally recognized as a negative regulator of the inflammatory response induced by infections, because it inhibits the activation of caspase-1 in inflammasome complexes, the production of the pro-inflammatory cytokines IL-1β and IL-18 and the overall response to sepsis.
Here, we report that GBPs control inflammation and sepsis in mice injected with either free LPS or purified OMVs derived from Gram-negative <i>Escherichia coli</i> In agreement with our observations from <i>in vivo</i> experiments, we demonstrate that macrophages lacking GBP2 expression fail to induce pyroptotic cell death and proinflammatory interleukin-1β (IL-1β) and IL-18 secretion when exposed to OMVs.
In response to pathogen infection, pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, IL-18 and tumor necrosis factor-α (TNF-α)] and anti-inflammatory cytokine (IL-10) increased in patients with sepsis.
In samples from four clinical centers, IL-18 was elevated in the plasma of patients with ARDS (sepsis or trauma-induced ARDS) and served as a novel biomarker of intensive care unit morbidity and mortality.
More importantly, AS101 downregulates IL-18 and IL-1beta serum levels in a mouse model of lipopolysaccharide (LPS)-induced sepsis, resulting in increased survival.
Patients who developed sepsis (n = 33) had higher interleukin (IL)-6, IL-18, and monocyte chemotactic protein-1 (MCP-1) concentrations at admission than patients (n = 27) who did not develop sepsis.
Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still's disease.
The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is a multimeric protein complex that mediates maturation of the cytokines IL-1β and IL-18 as well as release of the proinflammatory protein high-mobility group box 1 (HMGB1) and contributes to several inflammatory diseases, including sepsis, gout, and type 2 diabetes.
TNFRp55(-/-), IL-12p40(-/-), and IL-18(-/-) mutant mice, in which the Yersinia wild-type strain causes severe systemic infections, were used to investigate whether these Yersinia mutant strains would be attenuated in immunodeficient hosts.
We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588).
While recent investigations provide mechanistic evidence for a contribution of IL-18 to (hyper)inflammation in sepsis and MAS, we sought to study regulatory mechanisms underlying human IL-18 expression.