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Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System
Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa
Division of Pulmonology, Department of Internal Medicine, Steve Biko Pretoria Academic Hospital and Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
Division of Pulmonology, Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
* Author to whom correspondence should be addressed.
Received: 31 March 2010; in revised form: 26 April 2010 / Accepted: 24 May 2010 / Published: 25 May 2010
(This article belongs to the Special Issue Antibiotics
Abstract: In general antibiotics interact cooperatively with host defences, weakening and decreasing the virulence of microbial pathogens, thereby increasing vulnerability to phagocytosis and eradication by the intrinsic antimicrobial systems of the host. Antibiotics, however, also interact with host defences by several other mechanisms, some harmful, others beneficial. Harmful activities include exacerbation of potentially damaging inflammatory responses, a property of cell-wall targeted agents, which promotes the release of pro-inflammatory microbial cytotoxins and cell-wall components. On the other hand, inhibitors of bacterial protein synthesis, especially macrolides, possess beneficial anti-inflammatory/cytoprotective activities, which result from interference with the production of microbial virulence factors/cytotoxins. In addition to these pathogen-directed, anti-inflammatory activities, some classes of antimicrobial agent possess secondary anti-inflammatory properties, unrelated to their conventional antimicrobial activities, which target cells of the innate immune system, particularly neutrophils. This is a relatively uncommon, potentially beneficial property of antibiotics, which has been described for macrolides, imidazole anti-mycotics, fluoroquinolones, and tetracyclines. Although of largely unproven significance in the clinical setting, increasing awareness of the pro-inflammatory and anti-inflammatory properties of antibiotics may contribute to a more discerning and effective use of these agents.
Keywords: anti-inflammatory; fluoroquinolones; imidazole anti-mycotics; macrolides; mucociliary escalator; pattern recognition receptors; pro-inflammatory; tetracyclines
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Anderson, R.; Tintinger, G.; Cockeran, R.; Potjo, M.; Feldman, C. Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System. Pharmaceuticals 2010, 3, 1694-1710.
Anderson R, Tintinger G, Cockeran R, Potjo M, Feldman C. Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System. Pharmaceuticals. 2010; 3(5):1694-1710.
Anderson, Ronald; Tintinger, Gregory; Cockeran, Riana; Potjo, Moliehi; Feldman, Charles. 2010. "Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System." Pharmaceuticals 3, no. 5: 1694-1710.