Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tumor necrosis factor alpha (TNF-alpha) -308 G/A and TNF-beta NcO1 polymorphisms have been described to be associated with an increased risk for sepsis in critically ill patients. Functional consequences associated with these polymorphisms remain unclear. We compared the genotype distribution of these TNF polymorphisms with susceptibility to severe sepsis and leukocyte function in blunt trauma patients (n = 70; mean injury severity score, 24 points [range, 4 to 57). Severe sepsis was defined according to the American College of Chest Physicians-Society of Critical Care Medicine consensus conference criteria. Genotyping for the NcO1 polymorphism (alleles TNFB1 and TNFB2) was performed by PCR and digestion of the products with NcO1, and that for the TNF-alpha -308 G/A polymorphism (alleles TNF1 and TNF2) was performed by real-time PCR. Leukocyte function was assessed by measurement of the production of endotoxin-induced cytokines (TNF-alpha, interleukin-6 [IL-6], and IL-8) in whole blood. TNF-alpha, IL-6, and IL-8 were determined by enzyme-linked immunosorbent assay. For the genotypes of the TNF-alpha -308 G/A polymorphism, differences in the frequency of development of severe sepsis were not detectable. Patients developing severe sepsis after trauma were significantly more likely to possess a homozygous genotype of the TNF-beta NcO1 polymorphism. Compared with heterozygotes, the odds ratio for the TNFB2/B2 genotype for the development of severe posttraumatic sepsis was 11 (P = 0.01), and that for the TNFB1/B1 genotype was 13 (P = 0.014). TNF-alpha -308:TNF-beta NcO1 haplotype analysis showed that the TNFB2:TNF2 haplotype is significantly negatively associated with development of severe sepsis. Patients homozygous for the TNFB1 or TNFB2 allele showed a persistently higher cytokine-producing capacity during at least 4 to 8 days after trauma than the heterozygotes. In patients homozygous for the TNF1 allele, a higher TNF-alpha- and IL-8-producing capacity was found only at day 1 after trauma. Although the TNF-beta NcO1 polymorphism appears to be less likely to be causative for development of severe sepsis after trauma, it is thus far the only genetic marker identified which can be used as a relevant risk estimate for severe sepsis in trauma patients immediately after the injury.
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PMID:Tumor necrosis factor gene polymorphisms, leukocyte function, and sepsis susceptibility in blunt trauma patients. 1241 51

Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many water-soluble mediators with pro- and anti-inflammatory action such as TNF, IL-6, IL-8, and IL-10 play a strategic role in septic syndrome. In intensive care medicine, blocking any one mediator has not led to a measurable outcome improvement in patients with sepsis. CRRT is a continuously acting therapy, which removes in a nonselective way pro- and anti-inflammatory mediators; "the peak concentration hypothesis" is the concept of cutting peaks of soluble mediators through continuous hemofiltration. Furthermore, there is evidence of increased efficacy of high-volume hemofiltration compared to conventional CVVH, and other blood purification techniques that utilize large-pore membranes or sorbent plasmafiltration are conceptually interesting.
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PMID:Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. 1294 Sep 1

Severe sepsis and trauma complicated with multiple organ dysfunction syndrome (MODS) are among the leading causes of death in intensive therapy units, with mortality rate exceeding 50%. The outcome is not determined only by infection or trauma, but also by the intensity of immuno-inflammatory response, which is essential for host defence, but if uncontrolled leads to MODS. Pro-inflammatory cytokines (tumor necrosis factor-alpha--TNF-alpha, IL-1, IL-8, IL-12, IFN-gamma, etc.) represent a part of this immuno-inflammatory response to an insult. The results of the clinical investigation of correlation between pro-inflammatory cytokines (IL-8, IL-12, TNF-alpha, IFN-gamma), the outcome (survivors, non-survivors), and the severity (systemic inflammatory response syndrome--SIRS--less severe, and MODS--more severe) in polytraumatised patients with sepsis are presented in this paper. Mean values of IL-8 were 1.3-fold higher in non-survivors (p<0.05), and 60-fold higher in MODS group (p<0.01). Mean values of IL-12 were 1.6-fold higher in survivors (p<0.01), while the values between SIRS and MODS group did not differ significantly; mean values of TNF-alpha were 3-fold higher in survivors (p<0.05), and 46-fold higher in MODS group (p<0.01). Mean values of IFN-gamma did not differ significantly between the two groups regarding the outcome and severity. The obtained results indicated that IL-8 was a reliable predictor of lethal outcome and MODS (p<0.01), IL-12 a reliable predictor of survival (p<0.05), and TNF-alpha a reliable predictor of survival (p<0.05) and MODS (p<0.01).
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PMID:[Importance of determination of proinflammatory cytokines in the blood of polytraumatized patients with sepsis]. 1529 18