Association of IL-10 polymorphism with severity of illness in community acquired pneumonia

Gallagher, Paula; Lowe, Gregory; Fitzgerald, Tony; Bella, Anna Maria; Greene, Catherine M.; McElvaney, Noel G.; O’Neill, Shane

doi:10.1136/thorax.58.2.154

Cited by 185 publications

(101 citation statements)

References 8 publications

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“…An important strength of our study is the cohort design compared with earlier case-control designs (39,40). Designing studies to ascertain the role of genetic variants in susceptibility to infection poses several challenges.…”

Section: Discussionmentioning

confidence: 99%

4G/5G Plasminogen Activator Inhibitor-1 Polymorphisms and Haplotypes Are Associated with Pneumonia

Yende¹,

Angus²,

Ding³

et al. 2007

Am J Respir Crit Care Med

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Rationale: Plasminogen activator inhibitor (PAI)-1 inhibits urokinase and tissue plasminogen activator, required for host response to infection. Whether variation within the PAI-1 gene is associated with increased susceptibility to infection is unknown. Objectives: To ascertain the role of the 4G/5G polymorphism and other genetic variants within the PAI-1 gene. We hypothesized that variants associated with increased PAI-1 expression would be associated with an increased occurrence of community-acquired pneumonia (CAP). Methods: Longitudinal analysis (.12 yr) of the Health, Aging, and Body Composition cohort, aged 65-74 years at start of analysis. Measurements and Main Results: We genotyped the 4G/5G PAI-1 polymorphism and six additional single nucleotide polymorphisms. Of the 3,075 subjects, 272 (8.8%) had at least one hospitalization for CAP. Among whites, variants at the PAI4G,5G, PAI2846, and PAI7343 sites had higher risk of CAP (P 5 0.018, 0.021, and 0.021, respectively). At these sites, variants associated with higher PAI-1 expression were associated with increased CAP susceptibility. Compared with the 5G/5G genotypes at PAI4G,5G site, the 4G/4G and 4G/5G genotypes were associated with a 1.98-fold increased risk of CAP (95% confidence interval, 1.2-3.2; P 5 0.006). In whole blood stimulation assay, subjects with a 4G allele had 3.3-and 1.9-fold increased PAI-1 expression (P 5 0.043 and 0.034, respectively). In haplotype analysis, the 4G/G/C/A haplotype at the PAI4G,5G, PAI2846, PAI4588, and PAI7343 single nucleotide polymorphisms was associated with higher CAP susceptibility, whereas the 5G/G/C/A haplotype was associated with lower CAP susceptibility. No associations were seen among blacks. Conclusions: Genotypes associated with increased expression of PAI-1 were associated with increased susceptibility to CAP in elderly whites.

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Section: Discussionmentioning

confidence: 99%

4G/5G Plasminogen Activator Inhibitor-1 Polymorphisms and Haplotypes Are Associated with Pneumonia

Yende¹,

Angus²,

Ding³

et al. 2007

Am J Respir Crit Care Med

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“…The severity of pneumonia is both reflected and predicted by higher levels of cytokines in blood [16,[19][20][21][22]. Polymorphisms within the genes coding for cytokine expression are also associated with severity of disease [14,[23][24][25][26][27][28][29].…”

mentioning

confidence: 99%

Systemic cytokine response in patients with community-acquired pneumonia

Endeman¹,

Meijvis²,

Rijkers³

et al. 2010

European Respiratory Journal

105

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The role of individual cytokines and polymorphisms in pneumonia has been described, but the relationship between different cytokines and polymorphisms in relation to causative microorganisms, antibiotics, corticosteroids and clinical course has not. This study questions the relationship between cytokines, polymorphisms and clinical characteristics of pneumonia.Patients diagnosed with pneumonia were included in the study. Serum cytokine levels were measured during hospital stay, genotyping was performed, causative microorganisms were identified and patients were monitored throughout the hospital stay.In 201 patients with pneumonia interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-8 and IL-10 acted as acute phase proteins. After admission, the levels of these cytokines decreased rapidly. Single nucleotide polymorphisms did not influence cytokine production and were not associated with clinical outcome. Cytokine serum levels were significantly higher in patients with pneumococcal pneumonia. The decrease in levels of cytokines was independently influenced by the start of corticosteroid therapy.IL-1RA, IL-6, IL-8 and IL-10 are acute phase proteins, independent of genotype. Their levels are influenced by the nature of the causative microorganism and the start of corticosteroids therapy.

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“…IL-6 also had a high predictive value for late TF also (66). Interestingly studies suggest that genetic variability in the production of pro-inflammatory cytokines, in particular higher production of TNF alpha, IL-6, or the anti-inflammatory IL-10 is associated with higher mortality in sepsis including CAP (81,82). A large ICU based observational study verified that an IL-6 174 GG genotype was associated with less ARDS, Septic shock and MODs disease in ICU patients with CAP (83).…”

Section: Novel Biomarkersmentioning

confidence: 89%

Predictors of treatment failure and clinical stability in patients with community acquired pneumonia

Morley¹,

Torres²,

Cillóniz³

et al. 2017

Ann. Transl. Med.

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Community acquired pneumonia (CAP) is the leading infectious cause of mortality worldwide with approximately 10% of patients hospitalized requiring intensive care unit (ICU) admission. The ability to predict clinical stability (CS) and treatment failure (TF) enables the clinician to alter antibiotics appropriately, facilitate a timely ICU admission, or arrange a suitable discharge. The detection of CS and TF can be difficult and changes in clinical signs may be subtle or delayed. Thus clinical scores and biomarkers are routinely used to identify severity and monitor clinical progression. The evidence, however, is vast and the definitive role of these systems is at times difficult to elucidate. The aim of this review is to analyse the current literature and to provide a rational and clinically focused view of the predictive utility of various systems used to identify CS and TF in CAP.

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Association of IL-10 polymorphism with severity of illness in community acquired pneumonia

Cited by 185 publications

References 8 publications

4G/5G Plasminogen Activator Inhibitor-1 Polymorphisms and Haplotypes Are Associated with Pneumonia

4G/5G Plasminogen Activator Inhibitor-1 Polymorphisms and Haplotypes Are Associated with Pneumonia

Systemic cytokine response in patients with community-acquired pneumonia

Predictors of treatment failure and clinical stability in patients with community acquired pneumonia

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