Sepsis is the leading cause of death in critically ill patients and is the most common
risk factor for the development of acute lung injury in medical patients. Initially
investigators hypothesized that an excessive proinflammatory response contributed
to the pathogenesis of sepsis. However, this hypothesis overlooked the beneficial
effects of proinflammatory mediators and the detrimental effects of an excessive anti-inflammatory
response. This has led to a new hypothesis where sepsis is characterized by imbalances
of the pro- and anti-inflammatory responses, with tissue injury the result of an excessive
proinflammatory response and impaired pulmonary host defense the result of an excessive
anti-inflammatory response. This article reviews clinical studies and animal models
which show that sepsis results in an impaired lung host response to bacteria. Information
in this article should provide the reader with an increased understanding of the pathogenesis
of sepsis and the realization that new therapeutic strategies for sepsis need to take
into account the need to balance pro- and anti-inflammatory responses to maintain
pulmonary host defenses and prevent the development of acute lung injury.
KEYWORDS
Sepsis - innate immunity - pulmonary host defenses
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Charles W FrevertD.V.M. Sc.D.
VA Puget Sound Medical Center
GMR151-L, 1660 South Columbian Way
Seattle, WA
Email: cfrevert@u.washington.edu