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Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis

Authors Ginsburg I, Korem M, Koren E, Varani J

Received 7 October 2018

Accepted for publication 5 December 2018

Published 23 January 2019 Volume 2019:12 Pages 35—47

DOI https://doi.org/10.2147/JIR.S190007

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Ning Quan


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


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