Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis
Isaac Ginsburg,1 Maya Korem,2 Erez Koren,3 James Varani4 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel; 2Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Research and Deve...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-01-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/pro-inflammatory-agents-released-by-pathogens-dying-host-cells-and-neu-peer-reviewed-article-JIR |
| _version_ | 1818733886827397120 |
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| author | Ginsburg I Korem M Koren E Varani J |
| author_facet | Ginsburg I Korem M Koren E Varani J |
| author_sort | Ginsburg I |
| collection | DOAJ |
| description | Isaac Ginsburg,1 Maya Korem,2 Erez Koren,3 James Varani4 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel; 2Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Research and Development Department, Clexio Biosciences Ltd, Petah Tikva, Israel; 4Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI, USA Abstract: We postulate that the extensive cell and tissue damage inflicted by many infectious, inflammatory and post-inflammatory episodes is an enled result of a synergism among the invading microbial agents, host neutrophils and dead and dying cells in the nidus. Microbial toxins and other metabolites along with the plethora of pro-inflammatory agents released from activated neutrophils massively recruited to the infectious sites and high levels of cationic histones, other cationic peptides, proteinases and Th1 cytokines released from activated polymorphonuclear neutrophils (PMNs) and from necrotized tissues may act in concert (synergism) to bring about cell killing and tissue destruction. Multiple, diverse interactions among the many potential pro-inflammatory moieties have been described in these complex lesions. Such infections are often seen in the skin and aerodigestive tract where the tissue is exposed to the environment, but can occur in any tissue. Commonly, the tissue-destructive infections are caused by group A streptococci, pneumococci, Staphylococcus aureus, meningococci, Escherichia coli and Shigella, although many other microbial species are seen on occasion. All these microbial agents are characterized by their ability to recruit large numbers of PMNs. Given the complex nature of the disease process, it is proposed that, to treat these multifactorial disorders, a “cocktail” of anti-inflammatory agents combined with non-bacteriolytic antibiotics and measures to counteract the critical toxic role of cationic moieties might prove more effective than a strategy based on attacking the bacteria alone. Keywords: synergism, tissue damage, bacterial toxin, bacteriolysis, cationic proteins, sepsis |
| first_indexed | 2024-12-17T23:56:36Z |
| format | Article |
| id | doaj.art-5a794d118e5140febf0494bcb18887bd |
| institution | Directory Open Access Journal |
| issn | 1178-7031 |
| language | English |
| last_indexed | 2024-12-17T23:56:36Z |
| publishDate | 2019-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj.art-5a794d118e5140febf0494bcb18887bd2022-12-21T21:28:03ZengDove Medical PressJournal of Inflammation Research1178-70312019-01-01Volume 12354743725Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesisGinsburg IKorem MKoren EVarani JIsaac Ginsburg,1 Maya Korem,2 Erez Koren,3 James Varani4 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel; 2Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Research and Development Department, Clexio Biosciences Ltd, Petah Tikva, Israel; 4Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI, USA Abstract: We postulate that the extensive cell and tissue damage inflicted by many infectious, inflammatory and post-inflammatory episodes is an enled result of a synergism among the invading microbial agents, host neutrophils and dead and dying cells in the nidus. Microbial toxins and other metabolites along with the plethora of pro-inflammatory agents released from activated neutrophils massively recruited to the infectious sites and high levels of cationic histones, other cationic peptides, proteinases and Th1 cytokines released from activated polymorphonuclear neutrophils (PMNs) and from necrotized tissues may act in concert (synergism) to bring about cell killing and tissue destruction. Multiple, diverse interactions among the many potential pro-inflammatory moieties have been described in these complex lesions. Such infections are often seen in the skin and aerodigestive tract where the tissue is exposed to the environment, but can occur in any tissue. Commonly, the tissue-destructive infections are caused by group A streptococci, pneumococci, Staphylococcus aureus, meningococci, Escherichia coli and Shigella, although many other microbial species are seen on occasion. All these microbial agents are characterized by their ability to recruit large numbers of PMNs. Given the complex nature of the disease process, it is proposed that, to treat these multifactorial disorders, a “cocktail” of anti-inflammatory agents combined with non-bacteriolytic antibiotics and measures to counteract the critical toxic role of cationic moieties might prove more effective than a strategy based on attacking the bacteria alone. Keywords: synergism, tissue damage, bacterial toxin, bacteriolysis, cationic proteins, sepsishttps://www.dovepress.com/pro-inflammatory-agents-released-by-pathogens-dying-host-cells-and-neu-peer-reviewed-article-JIRSynergismtissue damagebacterial toxinbacteriolysiscationic proteinssepsis |
| spellingShingle | Ginsburg I Korem M Koren E Varani J Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis Journal of Inflammation Research Synergism tissue damage bacterial toxin bacteriolysis cationic proteins sepsis |
| title | Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis |
| title_full | Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis |
| title_fullStr | Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis |
| title_full_unstemmed | Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis |
| title_short | Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis |
| title_sort | pro inflammatory agents released by pathogens dying host cells and neutrophils act synergistically to destroy host tissues a working hypothesis |
| topic | Synergism tissue damage bacterial toxin bacteriolysis cationic proteins sepsis |
| url | https://www.dovepress.com/pro-inflammatory-agents-released-by-pathogens-dying-host-cells-and-neu-peer-reviewed-article-JIR |
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