Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. The J5 Study Group.
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.
Girardin
E
E
Department of Pediatrics, Hôpital Cantonal, Geneva, Switzerland.
Roux-Lombard
P
P
Grau
G E
GE
Suter
P
P
Gallati
H
H
Dayer
J M
JM
D016470:Bacteremia / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008585:Meningitis, Meningococcal / Q000097:blood* / Q000276:immunology / Q000401:mortality; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha