Respiratory syncytial virus (RSV) infection of airway epithelial cells stimulates the expression and secretion of a variety of cytokines including the chemotactic cytokines interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and RANTES (regulated upon activation, normal T cell expressed and secreted).
Interleukin-8, growth-related peptide-alpha, and monocyte chemotactic protein-1 were constitutively released by uninfected epithelial cells and were not further enhanced by infection with RSV.
A549 cells were infected with RSV, with or without GSPE pretreatment, and cultured for 24, 48 and 72 h. The expression of interleukin (IL)‑1β, IL‑6 and IL‑8, were measured by reverse transcription‑quantitative polymerase chain reaction, ELISA and western blotting.
Addition of the glucocorticoid anti-inflammatory agent hydrocortisone (200-1000 ng/ml) attenuated the production of MIP-1alpha and IL-8 in PIV-infected cells while having minimal to no effect on the production of these mediators from cells infected with RSV.
Among the cytokines associated with hRSV disease severity, IL-8, interferon-alpha (IFN-alpha), and IL-6, as well as the Th2-type cytokines thymic stromal lymphopoietin (TSLP), IL-3, and IL-33 have been highlighted as molecules with prognostic value in hRSV infections.
Cellular co-culture experiments performed with A549 cells and polymorphonuclear granulocytes or peripheral blood mononuclear cells revealed that increased IL-8 amounts were secreted in the co-culture of non-infected as well as RSV-infected cells.
Concentrations of TNF-a, IL-2, IL-5 and IL-8 on admission were significantly different from those of respiratory syncytial virus-positive children (n=28).
However, TNF, IL-1, and RSV, but not IL-6, induced IL-8 and IL-6 mRNA expression by the bronchial epithelial cells suggesting that cytokines produced by RSV-infected AM may be more important in modulating the inflammatory response in infection than directly interfering with virus infection/replication of airway epithelium.
In contrast, reduced respiratory syncytial virus-induced IL-8 responses and increased 5'-cytosine-phosphate-guanine-3' (CpG)-induced IL-12p40 and allergen-induced IL-4 responses were associated with atopy.
In summary, these experiments provide direct evidence for an autocrine mechanism of enhanced IL-8 production in RSV-infected epithelial cells that is primarily mediated by IL-1alpha.
No correlation between viral load and disease severity was observed however, there was a significantly lower concentration of the nasopharyngeal interleukin 8 (IL-8) in children with RV compared to HMPV and RSV, indicating a milder proinflammatory reaction.
OSC suppressed the RSV-increased production and release of pro-inflammatory cytokines and chemokines [tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, regulated on activation in normal T-cell expressed and secreted, macrophage inflammatory protein-1α; and monocyte chemoattractant protein-1] in A549 cells.
Outcome variables included: disease severity (infants requiring oxygen or ventilation were classified as having severe disease); RSV virus genotype (determined according to typing scheme based on the nucleoprotein and G glycoprotein genes); and amount of interleukin-8 mRNA in the nasopharyngeal aspirate, as measured by a semiquantitative polymerase chain reaction assay.
Overexpression of wt DCP1 led to a decrease in RSV-induced IL-8 production, but this effect was abrogated in cells overexpressing phosphorylation-deficient DCP1 mutants.
RSV-positive illnesses were associated with increased epithelial shedding, increased RANTES/protein ratios, and increased IL-8/protein ratios in NLF compared to RSV-negative illnesses.
The ability of replicating RSV to activate RelA translocation may play an important role in activating IL-8 and other inflammatory gene products necessary for airway mucosal inflammation seen in RSV disease.
The kinetics of cytokine production suggested that the RSV/CX3CR1 interaction induced RANTES (regulated on activation normal T-cell expressed and secreted protein), IL-8 and fractalkine production, whilst it downregulated IL-15, IL1-RA and monocyte chemotactic protein-1.
This study investigated whether IL-8 is in association with asthma and/or arthritis and whether the results can confirm a common genetic background of RSV bronchiolitis and asthma.
To test this hypothesis we compared immunoreactive IL-8 release by primary nasal epithelial cell (NEC) cultures established from young children with or without CF, at several time points after stimulation of cultures with tumor necrosis factor-alpha (TNF-alpha) or infection with respiratory syncytial virus (RSV).