These results indicate that S. aureus can down-regulate IL-8 release in endothelial cells through the secretion of inhibitory factor(s), and this may result in decreased neutrophil recruitment, thus interfering with the host immune response to bacterial infection.
An excessive neutrophilic inflammation, mainly orchestrated by the release of IL-8 from bronchial epithelial cells and amplified by chronic bacterial infection with Pseudomonas aeruginosa, leads to progressive tissue destruction.
The possible role of the proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor-alpha, IL-6, and IL-8 as modulators of host resistance to bacterial infections is discussed.
Elevated urine IL-8 level in kidney transplant patients with asymptomatic bacteriuria may reflect impaired immune response to bacterial infection and occult inflammatory process in urinary tract.
IL-1α and IL-1β were detectable in BAL in absence of infection, increased in the presence of bacterial infection and correlated with IL-8 (p < 0.0001), neutrophils (p < 0.0001) and NE activity (p < 0.01 and p < 0.001).
In summary, we describe a signaling pathway, Duox1-TACE-TGF-alpha-EGFR, on the surface of airway epithelial (NCI-H292) cells that mediates airway epithelial defense against bacterial infection by producing IL-8.
Finally, we revealed that agmatine diminishes IL-8 production by airway epithelial cells in response to bacterial infection, with a consequent decrease in neutrophil recruitment to the murine airways in an acute pneumonia model.
These results show that IL-8 overexpression in the bronchial epithelium benefits lung immunity to bacterial infection, but specifically drives lung damage through persistent inflammation, lung remodeling, and damaged tight junctions, leading to impaired lung function.