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 factor-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 36 months of age, febrile, nontoxic appearing, immunocompetent, no apparent bacterial source for fever on physical examination, and blood culture obtained. Additional blood, procured at the time of the blood culture, was analyzed by enzyme-linked immunosorbent assay for TNF, IL-1, and IL-6. Children with positive blood cultures for pathogenic bacteria served as cases. Two age-matched controls for each case were selected from the children with negative 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 moderate overlap in their ranges. TNF and IL-1 levels were not significantly different between cases and controls. Height of fever, duration of fever, acute illness observation score, absolute band count, and white blood cell count were all much less predictive of bacteremia than either IL-6 or absolute neutrophil count (ANC). The optimum IL-6 threshold value had a sensitivity 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 combination 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 100% sensitivity (95% CI, 33.0-infinity). For comparison, a WBC >15 x 10(9) cells/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 predictive of occult bacteremia than traditional tests and clinical criteria. The wide range in the IL-6 values for cases and controls detracts from the precision of the findings. The lack of rapid processing and clinical availability of IL-6 assays hampers its present application. However, despite these drawbacks and given the poor ability of traditional clinical and laboratory criteria to predict occult bacteremia, these results suggest a possible future role for IL-6 in predicting occult bacteremia when rapid assays become available.