INTERLEUKIN-6, BUT NOT TUMOR-NECROSIS-FACTOR-ALPHA, IS A GOOD PREDICTOR OF SEVERE INFECTION IN FEBRILE NEUTROPENIC AND NON-NEUTROPENIC CHILDREN WITH MALIGNANCY

Objective: Interleukin-6 (IL6), tumor necrosis factor-alpha (TNF-alpha ) and interferon-gamma (IFN-gamma) are important mediators of the infl ammatory response in human infection. The aim of this study was to det ermine the relationship between serum levels of IL6, TNF-alpha, IFN-ga mma and CRP in febrile children with malignant disease, and relate the se levels to aetiology of fever, presence of neutropenia and the effec t of untreated malignancy. Methods: 110 febrile episodes in 70 childre n with malignant disease were included. Cytokine analyses were perform ed with sensitive immunoradiometric methods using double monoclonal an tibodies. Results: IL6 had a sensitivity of 74% in detecting sepsis in children with fever and malignant disease. This sensitivity was not i nfluenced by the presence of neutropenia or newly diagnosed malignancy . A positive correlation between IL6 and the CRP levels on the followi ng day was observed (r = .53). TNF-alpha was elevated in 22% of the ep isodes and mean levels were significantly higher in untreated malignan cy but lower in neutropenic patients. IFN-gamma was elevated in 18% of cases and correlated strongly with mean TNF-alpha levels. Conclusions : IL6 is a sensitive and early predictor of bacterial infection in bot h neutropenic and non-neutropenic febrile children with malignancy. It is more sensitive than CRP in detecting sepsis, but the predictive va lue is too low to allow IL6 levels to influence initial treatment deci sions in patients with granulocytopenia. TNF-alpha production seems to be impaired in neutropenic children and serum TNF-alpha cannot be emp loyed as an indicator of bacterial infection.