The sepsis seesaw: tilting toward immunosuppression

Abstract

The immune response goes haywire during sepsis, a deadly condition triggered by infection. Richard S. Hotchkiss and his colleagues take the focus off of the prevailing view that the key aspect of this response is an exuberant inflammatory reaction. They assess recent human studies bolstering the notion that immunosuppression is also a major contributor to the disease. Many people with sepsis succumb to cardiac dysfunction, a process examined by Peter Ward. He showcases the factors that cause cardiomyocyte contractility to wane during the disease.

Figure 1

Immunologic response in sepsis over time. Although both pro- and anti-inflammatory responses are activated early in sepsis, the proinflammatory response predominates. As sepsis progresses, the anti-inflammatory response becomes predominant, and it is during this later phase that secondary infections and viral reactivation occur. Early deaths during the early proinflammatory response phase are due to cytokine storm–mediated events, whereas later deaths during the anti-inflammatory phase are due to failure to control pathogens.