The α7 nAChR partial agonist GTS-21 reduces secretion of pro-inflammatory cytokines including interleukin-6 (IL6) and tumor-necrosis factor (TNF) in models of endotoxemia and sepsis, and its anti-inflammatory effects are widely ascribed to α7 nAChR activation.
Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α.
Methane suppressed the expression of the toll-like receptor 4/nuclear factor-kappa B (NF-κB) signaling pathway and stimulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) during sepsis, which inhibited the activation of NF-κB and decreased the level of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, and interleukin-1β.
Plasma levels of miR-187 in sepsis patients were inversely correlated with those of TNF-α and IL-6 (r = -0.2841, -0.2163), and plasma levels of miR-21 and miR-145 were positively correlated with those of TNF-α and IL-6 (r = 0.615, 0.3057, 0.4465, 0.2734).
Here, results showed that pretreatment with rapamycin reduced the pyroptosis of peritoneal macrophages stimulated by cecal contents and the release of inflammatory factors such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α); In septic mice, rapamycin treatment decreased the activation of inflammasome in lung, and alleviated the pathological injuries in lung, liver and spleen tissues during acute stage of sepsis.
Impaired TNF-α production as a marker of sepsis-associated innate immune dysfunction may be a feasible target for immune stimulation to decrease time to organ failure recovery.
After excluding the compounds which are previously known to intervene sepsis or which show cytotoxicity to macrophages, the compounds which show dose-dependency in inhibiting the release of IL-6 and TNF-α by the OMV-stimulated macrophages in vitro and which reduce OMV-induced SIRS in vivo are selected.
In critically ill patients with sepsis induced AKI, serum TNF-α and uNAG measured at admission can predict severity of sepsis and AKI (defined by REFILE) occurrence along with pre-existing CKD and DM.
Change in DNA methylation pattern, histone modification, and microRNA regulation has been shown in sepsis models to silence or activate pro-inflammatory genes such as TNF-α and interleukins, anti-oxidant enzymes, and many signaling pathways.
T-lymphocyte subsets were detected by flow cytometer, the levels of tumor necrosis factor-α, interleukin-1 and calcitonin were determined by double-antibody immunoluminometric assay, and the effect of vitamin D on the above indicators in the treatment of sepsis was observed.
MALAT1 knockdown significantly increased LVSP and +dp/dsmax, decreased LVEDP and -dp/dsmax of sepsis as well as levels of cTn-I, CK, CK-MB, TNF-α, IL-1β, IL-6, IL-10, IL-17, IFN-γ, C5 and C5a.
We have reported a pivotal role for Nuclear Factors of Activated T cells (NFATc3) in regulating macrophage phenotype during sepsis induced ALI and subsequent studies demonstrate that NFATc3 transcriptionally regulates macrophage CCR2 and TNFα gene expression.
IL-38 administration decreased the inflammatory response, as reflected by lower levels of cytokines and chemokines (including IL-6, TNF-α, interleukin 10, interleukin 17, interleukin 27, CXCL1, and CCL2), and less damage to tissues (including lung, liver, and kidney) in CLP-induced sepsis.
Tumor necrosis factor (TNF)-α activates a diverse array of signaling pathways in vascular endothelial cells (ECs), leading to the inflammatory phenotype that contributes to the vascular dysfunction and neutrophil emigration in patients with sepsis.
The expression levels of AQP-5 in the sepsis group were significantly decreased compared with those in ctrl and SO groups (P<0.01), while the levels of TNF-α, IL-6 and p-P38 were significantly increased in sepsis group compared with those in ctrl and SO groups (P<0.01).
Bezafibrate treatment led to a reduction in leukocyte adherence, improved functional capillary density (FCD), and a reduction in interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α) and granulocyte macrophage colony stimulating factors (GM-CSF) plasma levels in experimental sepsis.
BTED for 6 hours significantly reduced the mRNA expression levels of tumor necrosis factor alpha (TNF-α) and IL-1β (all p < 0.05 vs. sepsis group), whereas mRNA expression of TNF-α and IL-1β in the intestine was increased after 6 hours' septic bile infusion compared with normal bile infusion group (all p < 0.05).
Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count.
Based on LPS induced sepsis model for the measurement of TNF-α inhibition in Swiss Albino mice and neutrophilia inhibition for asthma and COPD in Sprague Dawley rats with the potential molecules, compound 4 m would be great promise as a hit inhibitor in the future study.
PKCδ inhibition significantly reduced TNF-α-mediated hyperpermeability and TEER decrease in vitro in activated HBMVEC and rat brain in vivo 24 h after CLP induced sepsis.