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Amelioration of pathology by ELR-CXC chemokine antagonism in a swine model of airway endotoxin exposure.

Gordona JR; Zhang X; Li F; Nayyar A; Town J; Zhao X
J Agromedicine 2009 Apr; 14(2):235-241
Airborne organic dusts in swine confinement facilities have detrimental effects on workers health. Bacterial endotoxins (i.e., lipopolysaccharides [LPS]) that contaminate these dusts have been implicated in their pro-inflammatory effects in the airways. Exposure to such dusts induces expression of ELR-CXC chemokines (e.g., interleukin [IL]-8), prototypical neutrophil chemoattractants and activators, and neutrophilic pathology. To confirm the roles of the ELR-CXC chemokines in LPS-driven airway pathology, the authors exposed swine to bacterial LPS and tested whether blocking ELR-CXC chemokines would have beneficial effects. Delivery of the ELR-CXC chemokine antagonist CXCL8(3-74)K11R/G31P (G31P) blocked reactive oxygen intermediate production and chemotactic responses by IL-8-challenged neutrophils in vitro. In vivo, one treatment with G31P (100 µg/kg) blocked neutrophil inflammatory responses to intradermal LPS challenge for greater than or equal to 2 days. It also ameliorated pathology in piglets challenged via the airway with 1 mg of Eschericia coli LPS. On physical examination the saline-treated endotoxemic animals were depressed, pyrexic, and displayed labored breathing, whereas the G31P-treated animals were bright, active, and alert and had a low-grade fever and occasional cough. The lungs of the saline-treated animals displayed evidence of pleural surface hemorrhagic consolidation, and their airways contained large numbers of neutrophils (>80%) as well as substantial amounts of tumor necrosis factor (TNF) and IL-1. The G31P treatments of the LPS-challenged piglets reduced their airway neutrophilic inflammatory responses by approximately 86% and reduced the airway TNF (approximately 70%) and IL-1 (approximately 83%) levels. These data implicates the ELR-CXC chemokines in the neutrophilic inflammation observed after airways exposure to bacterial LPS.
Agricultural-industry; Agriculture; Airborne-dusts; Animal-studies; Bacterial-dusts; Confined-spaces; Environmental-exposure; Lung-disease; Lung-disorders; Lung-irritants; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Respiratory-hypersensitivity; Respiratory-infections; Respiratory-irritants; Toxicopathology; Toxins; Microorganisms; Endotoxins; Author Keywords: Airway; endotoxin; neutrophil; ELR-CXC chemokine; antagonist; G31P
Dr. John R. Gordon, Division of Respiratory, Critical Care and Sleep Medicine, Room 3610 Royal University Hospital, 103 Hospital Drive, Box 120 R.U.H, Saskatoon, Saskatchewan, Canada S7N 0W8
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Journal Article
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Journal of Agromedicine
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Marshfield Clinic
Page last reviewed: May 11, 2023
Content source: National Institute for Occupational Safety and Health Education and Information Division