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Updated: Aug 16, 2026

An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses
Published on: July 7, 2017
Interleukin-8: A pathogenetic role in antineutrophil cytoplasmic autoantibody-associated glomerulonephritis
P Cockwell1, C J Brooks, D Adu
1University of Birmingham, Edgbaston, Birmingham, England, United Kingdom.
Background:
In neutrophil trafficking, the role of interleukin-8 (IL-8) is location dependent. Tissue IL-8 directs transmigration, whereas intravascular IL-8 frustrates this process. The bystander damage of glomerular endothelium by antineutrophil cytoplasmic autoantibody (ANCA)-activated neutrophils is believed to be an early event in the pathogenesis of ANCA-associated glomerulonephritis. We have studied the role of IL-8 in this process.
Methods:
Intraglomerular expression of IL-8 in patients with ANCA-associated glomerulonephritis was studied by in situ hybridization and immunohistochemistry and location of neutrophils by serial section immunohistochemistry. In vitro, we analyzed ANCA-stimulated neutrophil IL-8 production by enzyme-linked immunosorbent assay, and the IL-8 attributable effect of ANCA-stimulated neutrophil supernatant by chemotactic and transendothelial assays.
Results:
There was intraglomerular expression of IL-8 at segmental, crescentic, and parietal epithelial sites. IL-8 protein expression colocalized to intraglomerular neutrophils; many localized within glomerular capillary loops, suggesting failed trafficking to tissue IL-8. ANCAs differentially stimulated time- and dose-dependent neutrophil IL-8 production, and ANCA-stimulated neutrophil supernatant demonstrated potent IL-8-dependent chemotactic activity and inhibited transendothelial migration of normal human neutrophils toward an IL-8 gradient.
Conclusion:
Despite heavy tissue expression of IL-8 in ANCA-associated GN, the production of IL-8 by ANCA-stimulated neutrophils within the intravascular compartment may frustrate neutrophil transmigration, encourage intravascular stasis, and contribute to bystander damage of glomerular endothelial cells.
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