Serum Levels Of Interleukins 6, 8, 10, MCP-1 And GCSF Are Risk Factors For Mortality In Children Admitted To The ICU With Influenza Infection

Abstract

To identify serum biomarkers predictive of death and near-death (ECMO) in children with life-threatening influenza infection. Objective:From January to August 2009, 22 sites in the PALISI Network enrolled 151 children admitted to the ICU with community Methods: acquired influenza infection. We collected extensive clinical data, performed multiplex viral PCR testing, collected serum and followed children to hospital discharge. Sera from 97 subjects were analyzed for a multiplex panel of 30 cytokines and chemokines using the Luminex platform as well as ELISA for IFNbeta. Results were interpolated from 5-parameter fits of standard curves using the corresponding recombinant proteins. All samples were analyzed in duplicate (coefficient of variation < 10%). We used linear and logistic regression to assess whether serum biomarkers on presentation were associated with severity of illness (PRISM III APS), death and death and/or ECMO.In the 97 children, 9 died and 3 additional children were ECMO survivors. Half of the sample (49%) had 2009 Pandemic H1N1 Results: (2009P-H1N1) and the other half had seasonal flu (70% influenza A, 30% influenza B). All analyses were adjusted for age, gender, underlying health conditions and immune compromise. Of the inflammatory mediators evaluated, serum MIP-1alpha and IL10 were strongly associated with illness severity (P=0.001, P=0.007). Serum levels of IL-6, IL-8, IL-10, GCSF MCP-1 and IP-10 were found to be strong risk factors for fatality (death or ECMO) (P=0.01 to 0.0008). IL-6, IL-8, IL-10, MCP-1 and GCSF were still significant (P=0.01 to 0.04) after additional adjustment for bacterial coinfection and PRISM APS. Addition of these serum biomarkers and clinical factors in a multivariate model predicting fatality (death or ECMO) increased the area under the ROC from 0.906 for clinical factors alone to 0.939 with addition of IL-6 and to 0.925 with addition of IL-8. After adjusting for age, gender and immune compromise, serum IL-2 was significantly higher in children with 2009P-H1N1 compared to those with seasonal flu (OR 2.79, 95% CI 1.58, 4.92, P = 0.0004).