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Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia.
E Girardin1, P Roux-Lombard, G E Grau
1Department of Pediatrics, Hôpital Cantonal, Geneva, Switzerland.
Abstract:
The extracellular domain of tumour necrosis factor-alpha (TNF-alpha) receptors have inhibitory properties against TNF-alpha. The relative ratio between ligand and ligand inhibitors may influence the outcome of meningococcaemia. To test this hypothesis, levels of TNF-alpha and of each of the soluble inhibitory fragments originating from two distinct TNF-alpha receptors (sTNF-RI and sTNF-RII) were measured in sera of children with severe meningococcaemia. On admission to the hospital the levels of sTNF-RI, -RII and TNF-alpha were markedly increased and all three correlated with the outcome of the disease. A correlation was found between TNF-alpha and sTNF-RI (P less than 0.001 by Pearson rank correlation coefficient) or sTNF-RII (P = 0.012). For TNF-alpha concentrations below 500 pg/ml, the increase of TNF-alpha was proportional to that of sTNF-RI and RII; however, when TNF-alpha levels exceeded 500 pg/ml, sTNF-RI and RII concentrations did not increase proportionally. At admission, in patients with fatal outcome, the ratios TNF-alpha/sTNF-RI and -RII were higher than in survivors. During the first 6 hr, the kinetics of TNF-alpha, sTNF-RI and -RII were different. Naturally occurring TNF-alpha inhibitors may play an important role in modulating the biological activity of TNF-alpha in severe meningococcaemia.
Insights
Tumour necrosis factor-alpha (TNF-alpha) inhibitors and TNF-alpha levels were measured in children with severe meningococcaemia. Higher ratios of TNF-alpha to its inhibitors correlated with fatal outcomes, suggesting a role in disease severity.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Tumour necrosis factor-alpha (TNF-alpha) receptors possess inhibitory functions against TNF-alpha.
- The balance between TNF-alpha and its soluble inhibitors may impact meningococcaemia outcomes.
Purpose of the Study:
- To investigate the relationship between TNF-alpha, soluble TNF-alpha receptor I (sTNF-RI), and soluble TNF-alpha receptor II (sTNF-RII) levels in severe meningococcaemia.
- To determine if the ratios of these molecules correlate with disease severity and patient outcomes.
Main Methods:
- Measurement of serum levels of TNF-alpha, sTNF-RI, and sTNF-RII in children with severe meningococcaemia upon hospital admission.
- Correlation analysis between the levels of these molecules and patient outcomes (survival vs. fatal outcome).
- Analysis of the kinetics and proportional changes of TNF-alpha and its soluble receptors.
Main Results:
- Marked increases in TNF-alpha, sTNF-RI, and sTNF-RII were observed in patients with severe meningococcaemia.
- All three molecules correlated with disease outcome.
- Higher ratios of TNF-alpha to sTNF-RI and sTNF-RII were found in patients with fatal outcomes compared to survivors.
- Disproportionate increases in sTNF-RI and sTNF-RII were noted when TNF-alpha levels exceeded 500 pg/ml.
Conclusions:
- Naturally occurring TNF-alpha inhibitors play a significant role in modulating TNF-alpha activity during severe meningococcaemia.
- The ratio of TNF-alpha to its soluble receptors is a potential indicator of disease severity and prognosis in meningococcaemia.