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Review
. 2021 May 14:8:628302.
doi: 10.3389/fmed.2021.628302. eCollection 2021.

Sepsis-Pathophysiology and Therapeutic Concepts

Dominik Jarczak  1 , Stefan Kluge  1 , Axel Nierhaus  1
Affiliations
Review

Sepsis-Pathophysiology and Therapeutic Concepts

Dominik Jarczak et al. Front Med (Lausanne). .

Abstract

Sepsis is a life-threatening condition and a global disease burden. Today, the heterogeneous syndrome is defined as severe organ dysfunction caused by a dysregulated host response to infection, with renewed emphasis on immune pathophysiology. Despite all efforts of experimental and clinical research during the last three decades, the ability to positively influence course and outcome of the syndrome remains limited. Evidence-based therapy still consists of basic causal and supportive measures, while adjuvant interventions such as blood purification or targeted immunotherapy largely remain without proof of effectiveness so far. With this review, we aim to provide an overview of sepsis immune pathophysiology, to update the choice of therapeutic approaches targeting different immunological mechanisms in the course of sepsis and septic shock, and to call for a paradigm shift from the pathogen to the host response as a potentially more promising angle.

Keywords: immune pathology; inflammation; sepsis; sepsis therapy; septic shock.

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Conflict of interest statement

DJ has received lecture honoraria and travel reimbursement from ADVITOS and CytoSorbents Europe GmbH. SK received research support from Ambu, Daiichi Sankyo, ETView Ltd., Fisher & Paykel, Pfizer and Xenios. He also received lecture fees from Astra, C. R. Bard, Baxter, Biotest, Cytosorbents, Daiichi Sankyo, Fresenius, Gilead, Mitsubishi Tanabe Pharma, MSD, Pfizer, Philips, and Zoll. He received consultant fees from Bayer, Fresenius, Gilead, MSD and Pfizer. AN has received lecture honoraria and travel reimbursement from ThermoFisher Scientific GmbH, CytoSorbents Europe GmbH and Biotest AG, Germany over the past 5 years. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Changes in pro- and anti-inflammatory response of the immune system during the course of sepsis and septic shock. HLA-DR, human leukocyte antigen-D related; IgM/G, immunoglobulin M/G; IL, interleukin; IFN-y, Interferon y; PAMPs, pathogen-associated molecular patterns; TNF-α, tumor necrosis factor alpha; TLR, toll-like receptor.
Figure 2
Figure 2
Overview of different aspects of immunological dysfunction with details of the affected entities. APC, antigen presenting cell; AZU1, azurocidine 1; CNC, circulating neutrophils count; CTSG, cathepsin G; ELANE, elastase; IFN-y, interferon y; Ig, immunoglobulin; MHCII, major histocompatibility complex II; MPO, myeloperoxidase; PD1, programmed death protein 1; TCR, T cell receptor. Adapted from Bermejo-Martin JF (12) with permission.
Figure 3
Figure 3
Currently available blood purification methods.
Figure 4
Figure 4
The central role of IgGAM in the innate and adaptive immune response. IFN, interferon; Ig, immunoglobulin; IgGAM, immunoglobulin G/A/M; IL, interleukin; NK cell, natural killer cell; Teff cell, effector T cell; TH cell, helper T cell; Treg cell, regulatory T cell.
See this image and copyright information in PMC

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