Sepsis-induced immune dysfunction: can immune therapies reduce mortality?
Matthew J. Delano, Peter A. Ward
Matthew J. Delano, Peter A. Ward
Published January 4, 2016
Citation Information: J Clin Invest. 2016;126(1):23-31. https://doi.org/10.1172/JCI82224.
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Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Abstract

Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after “recovery” from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical “recovery,” with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.

Authors

Matthew J. Delano, Peter A. Ward

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Figure 1

Historical and current sepsis mortality distribution.

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Historical and current sepsis mortality distribution. (A) Historically, ...
(A) Historically, sepsis deaths have occurred in a biphasic distribution, with an initial early peak at several days due to inadequate resuscitation, resulting in cardiac and pulmonary failure, and a late peak at several weeks due to persistent organ injury and failure. Considering the recent trend in sepsis outcomes, the elderly population, and mounting long-term mortality, a trimodal distribution may be more indicative of the current sepsis-associated death distribution. (B) The two early peaks in mortality exist, albeit with much lower magnitude than in the past. The third upswing occurs approximately 60 to 90 days after sepsis and continues to soar as time progresses. This delay in sepsis mortality is thought to be the consequence of the more sophisticated ICU care that keeps elderly and comorbidly challenged patients alive longer in spite of ongoing immune, physiologic, and biochemical aberrations.