Viral and bacterial sepsis: identification and characterization of cytokine profiles and cell death pathways
Date
2016-03-23
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Abstract
Sepsis and septic shock are the leading causes of death in intensive care units in North America.
Approximately 800,000 cases of sepsis are reported every year in the USA and 215,000 will
succumb to the disease despite aggressive antibiotic and supportive care [1-7]. The incidence of
sepsis is increasing at a rate of 9% per year even with advances in the understanding of the
pathophysiology of the disease [1]. Sepsis is commonly induced by bacterial and viral infections.
Influenza A is the virus that causes the flu. The most recent pandemic caused by Influenza A
(H1N1) demonstrated the potential of this virus to cause severe complications (viral induced
sepsis characterized by pneumonia, acute respiratory distress and acute lung injury). This study
investigated the inflammatory mediators of sepsis in H1N1 infected adults and from adults with
bacterial induced sepsis. For H1N1 infections lung tissue and sera samples were characterized.
Lung tissue showed hemorrhage, and interstitial congestion. Cytokine staining of these tissues revealed the presence of TNF-α, IFN-γ and IL-1β primarily from the recruited leukocytes. In
addition TUNEL assay revealed apoptosis occurring in these same cell populations. ELISA
quantification of sera from H1N1 infected adults also demonstrated high levels of TNF-α, IFN-γ
and IL-1β at 113 pg/mL, 49 pg/mL and 26 pg/mL respectively. The sera also were able to induce
apoptosis in cultured fibroblasts that was mediated through STAT1 signalling. The sera from
bacterial induced sepsis were characterized for the presence of other cytokines and chemokines.
TNF-α was consistently detected in all septic samples. Chemokine expression was more variable
across the septic samples. The identification of different mediators of inflammation during sepsis
will not only increase the basic knowledge about the progression of sepsis but would allow for
the development of biomarkers that could better predict the progression of sepsis to more severe
or fatal forms and allow for earlier intervention and treatment of these cases.
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Keywords
sepsis, inflammatory cytokines, H1N1 influenza A, viral pneumonia, apoptosis,, immunopathology