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Review
, 2018, 5086516
eCollection

The Central Role of the Inflammatory Response in Understanding the Heterogeneity of Sepsis-3

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Review

The Central Role of the Inflammatory Response in Understanding the Heterogeneity of Sepsis-3

Renyu Ding et al. Biomed Res Int.

Abstract

In sepsis-3, in contrast with sepsis-1, the definition "systemic inflammatory response" has been replaced with "dysregulated host response", and "systemic inflammatory response syndrome" (SIRS) has been replaced with "sequential organ failure assessment" (SOFA). Although the definition of sepsis has changed, the debate regarding its nature is ongoing. What are the fundamental processes controlling sepsis-induced inflammation, immunosuppression, or organ failure? In this review, we discuss the heterogeneity of sepsis-3 and address the central role of inflammation in the pathogenesis of sepsis. An unbalanced pro- and anti-inflammatory response, inflammatory resolution disorder, and persistent inflammation play important roles in the acute and/or chronic phases of sepsis. Moreover, powerful links exist between inflammation and other host responses (such as the neuroendocrine response, coagulation, and immunosuppression). We suggest that a comprehensive evaluation of the role of the inflammatory response will improve our understanding of the heterogeneity of sepsis.

Figures

Figure 1
Figure 1
The heterogeneity of sepsis-3. Once sepsis-3 was defined, its heterogeneity became apparent. The response to infection depends on the host and the pathogen, and dysregulated host responses are heterogeneous and complicated. SOFA, sequential organ failure assessment.
Figure 2
Figure 2
The heterogeneous inflammatory response in sepsis-3. According to the definition of sepsis-3, the dysregulated host response, as a bridge between the infection (the cause) and organ dysfunction (the outcome), is complicated and heterogeneous (a). In this review, we mainly discuss the central but heterogeneous role of the inflammatory response in sepsis. We propose a hypothetical classification of sepsis into “classical sepsis” (b) and “non-classical sepsis” (c). Hyperinflammation is regarded as the main cause of organ dysfunction in “classical sepsis” (b). Organ dysfunction might be caused by other host or noninfectious factors rather than hyperinflammation in “non-classical sepsis” (c). We believe that sepsis requires stratification and precise treatment. SIRS, systemic inflammatory response syndrome; SOFA, sequential organ failure assessment.
Figure 3
Figure 3
Two-phase model of sepsis-3. In the acute phase of sepsis, the host inflammatory response to an infection is heterogeneous, and sepsis may be classified as “classical” (hyperinflammation) and “non-classical” (hypoinflammation) (Figure 2). In the chronic phase of sepsis, persistent inflammation, immunosuppression, and catabolic syndrome (PICS) is the main cause of secondary infection and long-term mortality. CARS, compensatory anti-inflammatory response syndrome; DIC, disseminated intravascular coagulation; MODS, multiple organ dysfunction syndrome; SIRS, systemic inflammatory response syndrome; SOFA, sequential organ failure assessment. Adapted and modified from Hotchkiss et al. [3], Mira et al. [4], and Gentile et al. [5].

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