Cytokine Help for Diagnosing Community-Acquired Pneumonia*

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Among patients hospitalized for pneumonia, the use of antibiotics is based on a combination of clinical symptoms and radiographic findings unless culture results are available to guide treatment. This can result in either overuse of antibiotics and late recognition of patients who need them. In this issue of Pediatric Critical Care Medicine, Zhou and Ye (1) posit that admission serum interleukin (IL)-6 and IL-10 levels and the IL-6 to IL-10 ratio may aid in differentiation between pneumonia from typical bacterial, Mycoplasma pneumoniae (MP) and respiratory syncytial virus (RSV).
Many studies have attempted to identify biomarkers including various cytokines, procalcitonin, and C-reactive protein to predict pneumonia severity as well as to differentiate between etiologic microorganisms. IL-6, a marker of inflammatory activation, has been shown to correlate with illness severity in community-acquired pneumonia (CAP) and sepsis (2–6). IL-10, an anti-inflammatory cytokine, can be elevated in pneumonia but has not reliably correlated with severity of illness (2, 7). In general, the IL-6 to IL-10 ratio may represent a balance between pro- and anti-inflammatory elements of the immune response. Several studies have shown that the IL-6 to IL-10 ratio is increased in patients with more severe disease in pneumonia and sepsis (8–10).
The use of biomarkers to distinguish bacterial from viral CAP has been studied, however to date, none has proven to be consistently reliable and of sufficient specificity and sensitivity to be widely used. Many studies support procalcitonin as a biomarker potentially helpful in predicting bacterial from viral pneumonia (11, 12). The combination of markedly elevated C-reactive protein, WBC count, procalcitonin, and erythrocyte sedimentation rate was noted to increase the likelihood ratio for bacterial compared with viral pneumonia and viral compared with atypical pneumonia (13). Other studies have failed to show similar findings. Fewer studies have used cytokines such as IL-6 and IL-10 to discriminate between etiologies. One study showed that IL-6 was higher in pneumococcal versus nonpneumococcal pneumonia and another showed higher levels in bacterial versus RSV pneumonia (2, 14). The use of IL-10 to predict the etiology of CAP has not been reported. Overall, little progress has been made in identifying biomarkers to predict the etiology in CAP.
In their study, Zhou and Ye (1) measured serum IL-6 and IL-10 levels in children at hospital admission with CAP. They also assessed these patients for typical bacterial, MP, and RSV by bacterial culture, RSV polymerase chain reaction, and mycoplasma serology. In CAP patients who were diagnosed with one of these three etiologies, serum IL-6 and IL-10 levels and the ratio of IL-6 to IL-10 were significantly different. IL-6 was greater in bacterial than MP or RSV pneumonia and levels in MP were higher than RSV. IL-10 was greater in bacterial than MP and RSV and unlike IL-6, IL-10 was higher in RSV than MP. The authors reported that the sensitivity and specificity for IL-6 were remarkably high in differentiating between groups but did not report the same for IL-10 alone. The IL-6 to IL-10 ratio was higher in bacterial than MP and RSV pneumonia. Like IL-10, this ratio was lower in MP than RSV. The data presented here are robust, and the study has quite a large sample size for each etiology (166–180). As such, if these results are reproducible and generalizable, IL-6 and IL-10 levels may prove a useful test for guiding antibiotic therapy.
In analyzing the utility of such an assay, it will be important to determine the generalizability of the results presented here.

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