Imbalanced pro- and anti-Th17 responses (IL-17/granulocyte colony-stimulating factor) predict fatal outcome in 2009 pandemic influenza
© BioMed Central Ltd 2011
Published: 20 October 2011
Several clinical studies have confirmed an association between persistent hypercytokinemia and severe 2009 pandemic influenza, but none of these have used predictive models to analyze the relationship between the cytokines involved and disease outcome [1–4].
In the present work, we re-analyzed the results from two cohorts of critically ill patients suffering from pandemic influenza infection in 2009 [1, 2]. Thirty-five critically ill patients hospitalized with primary viral pneumonia were included in the analysis.
A beneficial role of IL-17 in lethal influenza has been previously proposed . In our experience, 9 out of the 10 patients who died had undetectable levels of IL-17. G-CSF is the principal cytokine controlling neutrophil development and function and could thus mediate excessive recruitment of neutrophils to the lungs, contributing to impairment of the respiratory system. In turn, G-CSF induces overexpression of negative regulators of Th17 differentiation . In fact, G-CSF levels correlated negatively with IL-17 levels in our cohort, supporting a potential inhibitory role of G-CSF on the secretion of IL-17 in these patients (Spearman r coefficient, -0.43; P-value 0.010).
In conclusion, IL-17 has been shown to be protective in severe pandemic influenza, while G-CSF is a risk factor for mortality, indicating the existence of imbalanced pro-and anti-Th17 responses during this disease.
granulocyte colony-stimulating factor
This work has been conducted by an international team pertaining to the Spanish-Canadian Consortium for the Study of Influenza Immunopathogenesis. The authors would like to thank also the nursing teams who kindly collected the samples and Lucia Rico and Veronica Iglesias for their precious laboratory assistance. The study was scientifically sponsored by the Spanish Society for Critical Care Medicine (SEMICYUC). Funding: Ministerio de Ciencia, MICCIN-FIS/JCYL-IECSCYL-SACYL (Spain); Programa de Investigación Comisionada en Gripe, GR09/0021-EMER07/050-PI081236-RD07/0067; National Institutes of Health (NIH), University Health Network and IDR Canada (DJK).
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