Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 levels in febrile, young children with and without occult bacteremia

Objective. To determine the utility of plasma levels of tumor necrosis fact or-alpha (TNF), interleukin 1 beta (IL-1), and interleukin 6 (IL-6) in the prediction of occult bacteremia in febrile, young children. Study Design. Prospective, case-control study conducted in a large, urban, children's hospital emergency department. Eligibility criteria were: 0 to 3 6 months of age, febrile, nontoxic appearing, immunocompetent, no apparent bacterial source for fever on physical examination, and blood culture obtai ned. Additional blood, procured at the time of the blood culture, was analy zed by enzyme-linked immunosorbent assay for TNF, IL-1, and IL-6. Children with positive blood cultures for pathogenic bacteria served as cases. Two a ge-matched controls for each case were selected from the children with nega tive cultures. Results. Out of 1329 enrollees, 33 cases and 66 controls were evaluated. IL -6 levels were significantly higher for the cases than controls but with mo derate overlap in their ranges. TNF and IL-1 levels were not significantly different between cases and controls. Height of fever, duration of fever, a cute illness observation score, absolute band count, and white blood cell c ount were all much less predictive of bacteremia than either IL-6 or absolu te neutrophil count (ANC). The optimum IL-6 threshold value had a sensitivi ty of 88%, a specificity of 70%, a positive predictive value (PPV) of 7.0%, a negative predictive value (NPV) of 99.6%, and an odds ratio (OR) of 16.7 (95% confidence interval [CI], 4.8-71.6). The optimum ANC threshold value had a sensitivity of 82%, a specificity of 74%, a PPV of 7.5%, a NPV of 99. 4%, and an OR of 12.8 (95% CI, 3.2-59.7). The best predictor was a combinat ion of IL-6 and ANC. It had a sensitivity of 100%, a specificity of 78%, a PPV of 10.4%, a NPV of 100%, and an OR which is undefined because of the 10 0% sensitivity (95% CI, 33.0-infinity). For comparison, a WBC >15 x 10(9) c ells/L had a sensitivity of 48%, a specificity of 79%, a PPV of 5.5%, a NPV of 98.3%, and an OR of 3.5 (95% CI, 1.1-10.7). Conclusions. In febrile children 0 to 36 months of age, IL-6 levels may be helpful in the prediction of occult bacteremia, but TNF and IL-1 levels are not. IL-6 levels alone or notably when combined with an ANC were more pred ictive of occult bacteremia than traditional tests and clinical criteria. T he wide range in the IL-6 values for cases and controls detracts from the p recision of the findings. The lack of rapid processing and clinical availab ility of IL-6 assays hampers its present application. However, despite thes e drawbacks and given the poor ability of traditional clinical and laborato ry criteria to predict occult bacteremia, these results suggest a possible future role for IL-6 in predicting occult bacteremia when rapid assays beco me available.