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Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) levels and IL-6, TNF-polymorphisms in children with
Selma Unal1, Fatma Gumruk, Selin Aytac
1Department of Pediatrics, Hacettepe University, Ankara, Turkey.
Insights
Infection history in children with thrombosis is linked to higher Interleukin-6 (IL-6) levels and specific IL-6 gene variations. These factors may increase the risk of developing thrombotic complications, particularly venous thrombosis.
Area of Science:
- Pediatric Thrombosis
- Immunology
- Genetics
Background:
- Infection is a significant factor in pediatric thrombosis pathogenesis.
- Elevated levels of tumor necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6) are suspected to increase thrombotic risk.
- Genetic variations in TNF-alpha and IL-6 promoter regions influence cytokine levels.
Purpose of the Study:
- To assess serum levels of C-reactive protein, TNF-alpha, and IL-6 in pediatric thrombosis patients.
- To investigate the association of TNF-alpha-308 G/A and IL-6-174 G/C polymorphisms with thrombosis in Turkish children.
- To explore the role of infection history in these associations.
Main Methods:
- Comparative analysis of serum cytokine and C-reactive protein levels.
- Genotyping for TNF-alpha and IL-6 promoter polymorphisms.
- Stratification of pediatric thrombosis patients based on infection history (within 15 days prior).
Main Results:
- Serum IL-6 levels were significantly higher in thrombotic children with a recent infection history compared to those without.
- The IL-6-174 C/C genotype was more prevalent in thrombotic children with a prior infection.
- TNF-alpha-308 G/A polymorphism distribution differed between infected and non-infected thrombotic children and controls.
- Venous thrombosis was more frequent than arterial thrombosis in children with an infection history.
Conclusions:
- A history of infection in pediatric thrombosis is associated with elevated IL-6 levels and the IL-6-174 C/C genotype.
- These findings suggest a potential link between infection, specific cytokine profiles, and thrombotic events in children.
- The IL-6-174 C/C genotype may be a risk factor for thrombosis in infected pediatric patients.
Abstract:
Infection has an important role in the pathogenesis of thrombosis and it becomes more prominent in childhood cases, in whom the infection frequency is higher. It has been suggested that patients with high tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels might be at increased risk of developing thrombotic complications owing to the effects of these cytokines on the coagulation pathway. Functional polymorphisms in the promoter regions of the genes coding for TNF-alpha and IL-6 are associated with increased plasma levels of these cytokines. The aims of this study were to evaluate the serum levels of acute phase reactants, such as C-reactive protein, and of cytokines (TNF-alpha and IL-6) and to investigate the association between the TNF-alpha-308 G/A and IL-6-174 G/C polymorphisms in Turkish pediatric patients with thrombosis. Fifty-eight children with thrombosis (group 1) and 89 controls (group 2) were included in the study. Patients who had a history of infection within the 15 days before thrombosis were classified as group 1a and those who had no infection history before thrombosis were classified as group 1b. Serum TNF-alpha did not differ significantly between the groups. However, the IL-6 level was higher in group 1a than in group 1b (P<0.05). The genotype distribution and allele frequencies of TNF-alpha G/A polymorphism were significantly higher in the thrombotic children without infection and in the control group than in the thrombotic children with an infection history (P<0.05). The IL-6-174 C/C genotype was significantly higher in thrombotic children with an infection history (P<0.05); there were no differences between the groups in mean allele frequency (Table 2). On the basis of our results, patients with a history of infection seem to have higher C-reactive protein and IL-6 levels and IL-6-174 C/C genotype. Furthermore, venous thrombosis is more frequent in this group than arterial thrombosis (P<0.05).
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