Is the Dosing and Timing of the Intervention Adequate?
During the last decade, major advances have been made in defining mechanisms of shock and organ injury due to infection. Intact host inflammatory responses are critical to limit and resolve serious infections. However, when these responses are intense they contribute to tissue injury and organ failure. Attempts to suppress inflammatory responses using corticosteroids or mediator-specific antagonists (e.g. tumor necrosis factor (TNF) antibodies) have either not improved survival or have been harmful in septic patients with life-threatening infections . The rationale for the use of anti-inflammatory agents in sepsis seems well founded. The proinflammatory cytokines TNF and IL-1 are detected during infections and when administered to humans or animals result in manifestations of shock. In some animal models, antagonists to TNF or IL-1 protect them from lethal bacterial challenge  . However, the inability to translate these observations into clinical use has led to a reassessment of this therapeutic approach.
KeywordsTumor Necrosis Factor Septic Shock Soluble Tumor Necrosis Factor Receptor Sepsis Trial Plasma Tumor Necrosis Factor
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