Genetic Polymorphisms, Functional Genomics and the Host Inflammatory Response to Injury and Inflammation

摘要

The term 'sepsis' refers to the host's systemic inflammatory response to an invasive microbial challenge; when the clinical constellation includes hypotension and/or concurrent end-organ injury, the condition is known as 'severe sepsis' or 'septic shock'. There are more than 750,000 cases and 100,000 deaths each year in the US alone attributable to sepsis and septic shock [1,2], translating into total costs of USD 16.7 billion annually [3], Overall, septic patients have a 25-45% mortality [1, 3,4]. The outcome of patients with sepsis and septic shock has improved minimally in the past 50 years, despite significant overall improvements in intensive care medicine. This systemic irinairunatory response, or more explicitly, the interplay between the microbial pathogen and the characteristics of host response, determines the magnitude and diversity of the host response, and ultimately outcome. A growing body of evidence is mounting to suggest that much of the host response is a direct reflection of heritabletraits, accounting for interpersonal differences, and allowing for genetic detection.