IL-6 gene polymorphisms and sepsis in icu adult romanian patients: a prospective study

Georgescu, Anca Meda; Bănescu, Claudia; Badea, Iudita; Moldovan, Valeriu; Huţanu, Adina; Voidăzan, Septimiu; Dobreanu, Minodora; Azamfirei, Leonard

doi:10.1515/rrlm-2016-0044

Cited by 13 publications

(14 citation statements)

References 42 publications

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“…The severity scores in this reference unit are significantly above the levels in other ICUs. Consequently, this also leads to much higher mortality rates, which is also reflected in previous sepsis studies [50,76,77].…”

Section: Discussionmentioning

confidence: 62%

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Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

et al. 2020

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Background: The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. Methods: We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A,-238G/A,-376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. Results: TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. Conclusions: TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

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Section: Discussionmentioning

confidence: 62%

“…The study was designed as a non-interventional prospective cohort study. The patients enrolled during the first 10 months of the study had been included in a previous report discussing interleukin IL-6 genetic variability in sepsis [50]. The previously reported inclusion and exclusion criteria were applied.…”

Section: Study Populationmentioning

confidence: 99%

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

et al. 2020

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“…Based on their inflammatory activity, cytokines are divided into pro‐inflammatory (IL‐6, IL‐17, IL‐18, TNF‐α, interferon gamma [IFN‐γ], etc) and anti‐inflammatory (Il‐4, IL‐10, IL‐13, etc) ones, whereas several cytokines have a dual role (IL‐10, IL‐22, TGF‐β1) . Interleukin‐10, an anti‐inflammatory cytokine, has dual functions, being both immune‐suppressive (tumor‐inhibiting) and immune‐stimulating (tumor‐promoting), and may, therefore, influence tumor susceptibility and development.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 Chronic inflammation is associated with the release of various mediators (pro-inflammatory and oncogenic ones), such as reactive nitrogen oxygen species, inflammatory cytokines (IL-1β, IL-2, IL-6, and tumor necrosis factor alpha [TNF-α]), growth factors, and chemokines. 4 Based on their inflammatory activity, cytokines are divided into pro-inflammatory (IL-6, IL-17, IL-18, TNF-α, interferon gamma [IFN-γ], etc) 5 and anti-inflammatory (Il-4, IL-10, IL-13, etc) ones, whereas several cytokines have a dual role (IL-10, IL-22, TGF-β1). 6 Interleukin-10, an anti-inflammatory cytokine, has dual functions, being both immune-suppressive (tumor-inhibiting) and immune-stimulating (tumor-promoting), and may, therefore, influence tumor susceptibility and development.…”

Section: Introductionmentioning

confidence: 99%

Cytokine rs361525, rs1800750, rs1800629, rs1800896, rs1800872, rs1800795, rs1800470, and rs2430561 SNPs in relation with prognostic factors in acute myeloid leukemia

et al. 2019

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Background Cytokines were correlated with survival and disease progression in acute myeloid leukemia (AML). We aimed to evaluate the multivariate effect of TNF‐α rs361525, rs1800750, rs1800629, IL‐10 rs1800896, rs1800872, IL‐6 rs1800795, TGF‐β1 rs1800470, IFN‐γ rs2430561 single nucleotide polymorphisms (SNPs) on AML risk, the multivariate effect of SNPs on overall survival (OS) in AML and the association between the investigated SNPs and prognostic factors in AML. Methods All SNPs were genotyped in 226 adult AML cases and 406 healthy individuals. AML patients were investigated for FLT3 (ITD, D835), DNMT3A (R882), and NPM1 type A mutations. Results Univariate analysis revealed that age above 65 years had a negative influence on survival (P < .001). The presence of the rs1800750 variant genotype (P = .005) or FLT3‐ITD mutation (P = .009) in a cytogenetic high‐risk group (P = .003) negatively influenced OS. A negative association was observed between Eastern Cooperative Oncologic Group Scale status > 2, lactate dehydrogenase (LDH) level, platelet (PLT) count <40 000 cells/mm3, and OS. Multivariate Cox regression analysis showed that the presence of the rs1800750 variant genotype was a risk factor for death (P = .007), and that blast percentage, LDH level (≥600 IU/L), and cytogenetic high‐risk were independent significant predictors for death in AML (P = .04, corrected HR = 1.20; P = .022, corrected HR = 1.24; P = .021, corrected HR = 1.34, respectively). Conclusions Age above 65 years, PLT count, TNF‐α rs1800750 variant genotype, blast percentage, LDH level, and cytogenetic high‐risk may be used as independent risk factors to assess AML mortality.

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“…IL-6 cytokine seems to be a promising biomarker in sepsis since it is involved in triggering and modulating the inflammatory response to microbial injury. Its fast dynamics, with a rapid increase of IL-6 levels in the early stages of sepsis are important features which make it a good biomarker for sepsis; surprisingly it is not routinely used [12].…”

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confidence: 99%

To Be or Not to Be… Sepsis? A Daily Challenge in ICU

Man

Grigorescu

2020

The Journal of Critical Care Medicine

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IL-6 gene polymorphisms and sepsis in icu adult romanian patients: a prospective study

Cited by 13 publications

References 42 publications

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

Cytokine rs361525, rs1800750, rs1800629, rs1800896, rs1800872, rs1800795, rs1800470, and rs2430561 SNPs in relation with prognostic factors in acute myeloid leukemia

To Be or Not to Be… Sepsis? A Daily Challenge in ICU

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