Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood.
Polymorphoneutrophil leucocytes (PMNLs) are implicated in the pathogenesis of diarrhea-associated hemolytic uremic syndrome (D+ HUS). We investigated mechanisms of PMNL involvement by measuring tumor necrosis factor alpha (TNF alpha) and the novel cytokine, interleukin-8 (IL-8), a potent activator of neutrophils, together with alpha 1- antitrypsin-complexed elastase (alpha 1-AT-E) as a marker of neutrophil degranulation, and anti-neutrophil cytoplasmic antibodies (ANCA). IL-8 was not detected in the 17 normal children, but was significantly elevated in 20 of 25 D+ HUS children (P less than 0.005), and in three of nine children with non-diarrhea-associated (D-) HUS. Sequential data showed that IL-8 peaked transiently in the circulation, reaching a maximum just before a more protracted burst of alpha 1-AT-E. The IL-8 levels correlated significantly with circulating alpha 1-AT-E concentrations (r = 0.50, P less than 0.05). In D+ HUS IL-8 levels also correlated with the PMNL count (r = 0.63, P less than 0.005), and the highest values were seen in those children who died in the acute phase of the disease. TNF alpha was raised in only 1 of 16 D+ HUS children and in no patients were ANCA detected. The data suggest that PMNLs in HUS are recruited by IL-8, that this cytokine plays a key role in the PMNL activation which occurs, and that agents which suppress this recruitment and activation might play a therapeutic role in this disorder.
Fitzpatrick
M M
MM
Medical Unit, Institute of Child Health, London, England, United Kingdom.
Shah
V
V
Trompeter
R S
RS
Dillon
M J
MJ
Barratt
T M
TM
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000032:analysis; D002648:Child; D003967:Diarrhea / Q000097:blood; D006463:Hemolytic-Uremic Syndrome / Q000097:blood*; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D007958:Leukocyte Count; D009504:Neutrophils / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D000515:alpha 1-Antitrypsin / Q000032:analysis
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin