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 Agromed 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
Journal of Agromedicine