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Figures
Fig. 1
Group cytokine concentrations. Patients are divided into 3 groups: (1) seasonal influenza, (2) H1N1 influenza, (3) bacterial pneumonia (PNA), and (4) other infection. Cytokines depicted are broken down into IL-4 (A), IL-5 (B), GM-CSF (C), IFNγ (D), and IL-6 (E). Stacked bars are means with error bars depicting 95% confidence intervals. Statistical significance highlighted by star (★).
Fig. 2
Interleukin 10 cytokine concentrations. Increased levels of IL-10 among both influenza groups (★) compared with bacterial pneumonia (PNA) and other respiratory infections. Stacked bars are means with error bars depicting 95% confidence intervals.
Fig. 3
Receiver operator characteristic curves for total WBC and cytokines IFNγ, GM-CSF, IL6, IL5, and IL4.
Fig. 4
Interleukin 6 levels among bacterial pneumonia patients who spent less than 72 hours (<3 days) vs greater than 72 hours (>3 days) in the hospital. Stacked bars are means with error bars depicting 95% confidence intervals. The y-axis for the more than 3 days group is to the left, whereas the y-axis for the less than 3 days group is to the right.
Abstract
Objective
The objective of this study is to characterize the cytokine response among patients presenting with an influenza-like illness who are infected with the influenza virus, a bacterial pneumonia, or another viral infection. We hypothesize that there are differences in proinflammatory and anti-inflammatory cytokines in relation to cytokines associated with the humoral response during viral and bacterial respiratory infections.
Methods
We enrolled adults who presented to an urban academic emergency department during the 2008 to 2011 influenza seasons with symptoms of fever and a cough. Subjects had nasal aspirates tested by viral culture, and peripheral blood drawn to quantify cytokine concentrations. Cytokine concentrations were compared between groups using the Wilcoxon rank sum test, and receiver operating characteristic curves were calculated.
Results
A total of 80 patients were enrolled: 40 with influenza infection, 14 patients with a bacterial pneumonia as determined by infiltrate on chest x-ray, and 26 patients negative for influenza infection and infiltrate. There were differences between the bacterial pneumonia group, and all other viral infections grouped together with regard to interleukin (IL) 4 (2.66 vs 16.77 pg/mL, P < .001), IL-5 (20.57 vs 57.57 pg/mL, P = .006), IL-6 (403.06 vs 52.69 pg/mL, P < .001), granulocyte macrophage colony-stimulating factor (18.26 vs 66.80 pg/mL, P < .001), and interferon γ (0.0 vs 830.36 pg/mL, P < .001). Interleukin 10 concentrations were elevated in patients with influenza (88.69 pg/mL) compared with all other groups combined (39.19 pg/mL; P = .003).
Conclusion
Cytokines IL-4, IL-5, IL-6, granulocyte macrophage colony-stimulating factor, and interferon γ may serve as distinct markers of bacterial infection in patients with an influenza-like illness, whereas IL-10 is uniquely elevated in influenza patients.
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☆Funding: This study was designed and carried out at Rhode Island Hospital/Brown University. Patient recruitment, viral testing, and sample storage were supported by an intradepartmental grant through the Department of Emergency Medicine. The cytokine assay was supported through the University of Massachusetts Medical School's Healey Endowment Grant.
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