Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokine-induced neutrophil chemoattractant (CINC) is a rat cytokine with structural and functional homology to human interleukin-8 (IL-8) and melanoma growth-stimulatory activity (MGSA/gro). We investigated the relationship between CINC and the production of chemotactic activity for neutrophils by rat alveolar macrophages after in vitro and in vivo treatment with endotoxin. After in vitro treatment with endotoxin, the chemotactic bioactivity produced by alveolar macrophages increased in a time- and dose-dependent manner. This increase in chemotactic activity was closely associated with increased levels of steady-state CINC mRNA. About 50% of the chemotactic activity was blocked by treatment with neutralizing concentrations of anti-CINC antibodies. We then evaluated the role of CINC in vivo in the development of neutrophilic alveolitis in rats, which results from a single intraperitoneal injection of endotoxin. In this model, peak numbers of neutrophils are recovered in lung lavage fluid 24 h after endotoxin injection. Steady-state CINC mRNA levels in the lung peaked 2 h after endotoxin injection. Many cytokines whose transcription is induced during sepsis, including IL-8 and MGSA/gro, are thought to be transcriptionally regulated by nuclear factor kappa B (NF-kappa B). The CINC gene contains a binding site in the promoter region for NF-kB. Therefore, we sought to determine whether NF-kappa B binding to the CINC NK-kappa B motif was increased in nuclear extracts from rat lung lavage cells after exposure to endotoxin using gel mobility shift assays. Increased nuclear NF-kappa B binding activity was detected 2.5 h after in vivo treatment with endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine-induced neutrophil chemoattractant mediates neutrophilic alveolitis in rats: association with nuclear factor kappa B activation. 791 14

Although sepsis causes significant morbidity and mortality, its basic pathology is still not well understood. We investigated the inflammatory and physiologic alterations of non-lethal sepsis using cecal ligation and puncture (CLP), a model that induces peritonitis due to mixed intestinal flora, reproducing the complex immunology of sepsis. Groups of mice were subjected to CLP (25G needle) or sham surgery, had minimitters implanted to continuously monitor temperature and activity, and were sacrificed daily for 6 days. There was significant hypothermia (6-13 hrs post-surgery), and decreases in activity (to day 4) and weight (to day 3) but no mortality in the CLP group. Blood analyses of the CLP-treated mice showed reduced hemoglobin, platelets, lymphocytes, monocytes, and neutrophils, compared to sham animals. Both groups had nearly equivalent neutrophil influx into the peritoneum. Plasma and peritoneal G-CSF, IL-6, as well as the murine chemokines KC and MIP2-alpha were significantly higher in the CLP-treated mice at day 1. Plasma and peritoneal TNF were low (<70 pg/mL). While there was elevated IL-1beta in the peritoneum of the CLP-treated mice, this cytokine was not detected in the plasma in either treatment group. Cytokines were not detected in the pulmonary airspace of the CLP-treated mice and PMNs were not recruited to this site. Our data shows altered immunopathology in non-lethal sepsis with significant blood and cytokine alterations. Since there was 100% survival, the inflammatory response was appropriate and probably even protective.
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PMID:Immunopathologic responses to non-lethal sepsis. 1044 92

Neutrophil specific chemokines are potent chemoattractants for neutrophils. IL-8/CXCL8 is the most extensively studied member of this group, and its concentrations increase during inflammatory conditions of the newborn infant including sepsis and chronic lung disease. A significant amount of information exists on the effects of IL-8/CXCL8 on neutrophil chemotaxis of neonates, but little is known about the other neutrophil specific chemokines. The aim of this study was to determine the relative potency of the neutrophil specific chemokines on chemotaxis of neonatal neutrophils and to compare this effect with the effect on adult neutrophils. Neutrophils were isolated from cord blood or healthy adult donors and incubated in a Neuroprobe chemotaxis chamber. Chemokine concentrations ranging from 1-1000 ng/mL were used. Differences in chemotactic potency existed among the seven neutrophil specific chemokines. Specifically, at 100 ng/mL, the order was IL-8/CXCL8>GRO-alpha/CXCL1>GCP-2/CXCL6>NAP-2/CXCL7>ENA-78/CXCL5>GRO-gamma/CXCL2>GRO-beta/CXCL3. This pattern was observed for adult and neonatal neutrophils. We conclude that (1) neutrophils from cord blood exhibit the same pattern of potency for each ELR chemokine as neutrophils from adults, and (2) migration of neonatal neutrophils is significantly less than that of adults at every concentration examined except the lowest (1 ng/mL).
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PMID:The effects and comparative differences of neutrophil specific chemokines on neutrophil chemotaxis of the neonate. 1561 81