Systemic cytokine response profiles associated with respiratory virus-induced acute otitis media.
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-1beta, -2, -4, -5, -6, -7, -8, -10, -12, -13, -17, granulocyte-colony stimulating factor (G-CSF), granulocyte-monocyte-colony stimulating factor, interferon-gamma, MCP-1, MIP-1beta, TNF-alpha) 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-gamma, 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.
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0371, USA.
Janak A
JA
Patel
Sangeeta
S
Nair
James
J
Grady
Krystal
K
Revai
Sundar
S
Victor
Allan R
AR
Brasier
Tasnee
T
Chonmaitree
D000208:Acute Disease; D001424:Bacterial Infections / Q000150:complications / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010033:Otitis Media / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D012141:Respiratory Tract Infections / Q000150:complications* / Q000821:virology*
D016207:Cytokines