Background: Acute otitis media (AOM) results from a complex interplay between the infectious agents and host immune responses. Cytokines play a major role in the pathogenesis of AOM, but there are few studies on the systemic cytokine response during AOM.
Methods: Sera were collected from 145 children (median age = 13.5 months) at the time of diagnosis of AOM. Concentrations of 17 cytokines (IL-1β, -2, -4, -5, -6, -7, -8, -10, -12, -13, -17, granulocyte-colony stimulating factor (G-CSF), granulocyte-monocyte-colony stimulating factor, interferon-γ, MCP-1, MIP-1β, TNF-α) were determined and correlated with viral etiology and clinical outcome. The statistical analysis was conducted using bioinformatics software.
Results: Cluster patterns of concentrations of cytokines were examined by unsupervised hierarchical clustering algorithms. Four major cluster groups were identified, one of the groups was significantly enriched for cases of respiratory syncytial virus (RSV)-induced AOM as compared with other viruses. Specifically, RSV-induced AOM had significantly higher concentrations of G-CSF, MCP-1, IL-10, IL-6, interferon-γ, and IL-8 (P < 0.05). Using a decision tree classifier, higher G-CSF concentrations produced 87.6% accuracy to predict RSV-induced AOM. Overall, higher IL-13 concentrations produced 84.2% accuracy to predict early clinical failure of antibiotic treatment.
Conclusions: Children with AOM have a unique pattern of systemic cytokine response that relates to virus etiology and clinical outcome. Based on G-CSF and IL-13 measurements, it is possible to accurately classify RSV-induced AOM and early treatment failure, respectively; these observations will need to be validated in an independent population.
From the *Department of Pediatrics, †Department of Preventive Medicine and Community Health, ‡Sealy Center for Molecular Medicine, and §Department of Internal Medicine, General Clinical Research Center, University of Texas Medical Branch, Galveston, TX.
Accepted for publication November 11, 2008.
Supported by the National Institutes of Health grant R01 DC 2620 (to T.C.); grant M01 RR 00073 from the National Center for Research Resources, NIH; and informatics support was partially provided by the Integrated Health Science Facility Core (P30 ES06676, to J. Halpert, UTMB).
Address for correspondence: Tasnee Chonmaitree, MD, Division of Pediatric Infectious Disease and Immunology, Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0371. E-mail: firstname.lastname@example.org.
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