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. 2010 Jul 1;363(1):87-9.
doi: 10.1056/NEJMcibr1004371.

Immunotherapy for sepsis--a new approach against an ancient foe

Richard S Hotchkiss  1 , Steven Opal
Affiliations

Immunotherapy for sepsis--a new approach against an ancient foe

Richard S Hotchkiss et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Reversal of Immunosuppression in Sepsis
Many patients fail to eradicate the initial invading pathogens and progress to a prolonged phase of sepsis-induced immunosuppression characterized by failure to eradicate the primary infection and development of secondary nosocomial infections. The immunosuppression is mediated by multiple mechanisms including massive apoptosis-induced depletion of lymphocytes and dendritic cells, decreased expression of the cell surface antigen presenting complex HLA-DR, and increased expression of negative co-stimulatory molecules programmed death 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), B and T lymphocyte attenuator (BTLA), and their corresponding ligands, e.g., (PD-L1). Furthermore, T-regulatory cells (T-regs) and myeloid-derived suppressor cells (MDSCs) are increased and there is a shift from an inflammatory Th1 phenotype to an anti-inflammatory Th2 lymphocyte phenotype with production of IL-10. The net result is a severely compromised innate and adaptive immune system with poorly functional “exhausted” CD8 and anergic CD4 T cells. Potential immunotherapeutic approaches (illustrated in red color) include agents that block apoptosis, block negative co-stimulatory molecules, decrease anti-inflammatory cytokines, increase HLA-DR expression, and reactivate “exhausted” or anergic T cells. Abbreviations: DC, dendritic cell; MAC, macrophage; PMN, polymorphonuclear leukocyte; FLT-3L, Fms-related tyrosine kinase 3 ligand, GM-CSF, granulocyte macrophage colony stimulating factor;
See this image and copyright information in PMC

References

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