Viral and bacterial sepsis: identification and characterization of cytokine profiles and cell death pathways

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.