Document Detail

Immune dysregulation in severe influenza.
MedLine Citation:
PMID:  19276177     Owner:  NLM     Status:  MEDLINE    
Among previously healthy children with severe influenza, the mechanisms leading to increased pathology are not understood. We hypothesized that children with severe influenza would have high levels of circulating cytokines. To examine this, we recruited patients with severe influenza and examined plasma cytokine levels as well as the ability of peripheral blood cells to respond to stimuli. Ten patients with severe influenza were enrolled during the 2005-2007 influenza seasons. We evaluated plasma cytokine levels, circulating NK cells, and responses to TLR ligands during the illness. We compared these patients with five patients with moderate influenza, six patients with respiratory syncytial virus (RSV), and 24 noninfected controls. Patients with influenza showed depressed responses to TLR ligands when compared with RSV patients and healthy controls (P<0.05). These normalized when retested during a convalescent phase. Plasma levels of IL-6, IL-12, and IFN- were elevated in influenza patients compared with controls (P<0.05). A compromised ability to produce TNF- was reproduced by in vitro infection, and the magnitude of the effect correlated with the multiplicity of infection and induction of IFN regulatory factor 4 expression. Aberrant, systemic, innate responses to TLR ligands during influenza infection may be a consequence of specific viral attributes such as a high inoculum or rapid replication and may underlie the known susceptibility of influenza-infected patients to secondary bacterial infections.
Meredith L Heltzer; Susan E Coffin; Kelly Maurer; Asen Bagashev; Zhe Zhang; Jordan S Orange; Kathleen E Sullivan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  85     ISSN:  1938-3673     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-04     Completed Date:  2009-06-17     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1036-43     Citation Subset:  IM    
Divisions of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
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MeSH Terms
Blotting, Western
Child, Preschool
Cytokines / blood
Flow Cytometry
Gene Expression Regulation
Immune System Diseases / complications,  immunology*,  physiopathology*
Influenza, Human / complications,  genetics,  immunology*,  physiopathology*
Interferon Regulatory Factors / metabolism
Killer Cells, Natural / immunology,  virology
Leukocytes, Mononuclear / virology
Natural Cytotoxicity Triggering Receptor 1 / immunology
Toll-Like Receptors / metabolism
Grant Support
Reg. No./Substance:
0/Cytokines; 0/Interferon Regulatory Factors; 0/NCR1 protein, human; 0/Natural Cytotoxicity Triggering Receptor 1; 0/Toll-Like Receptors; 0/interferon regulatory factor-4

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