Cilomilast Modulates Rhinovirus-Induced Airway Epithelial ICAM-1 Expression and IL-6, CXCL8 and CCL5 Production.

Cilomilast, a phosphodiesterase-4 (PDE4) selective inhibitor, has anti-inflammatory effects in vitro and in vivo and reduces COPD exacerbations. We tested the hypothesis that cilomilast inhibits virus-induced airway epithelial intercellular adhesion molecule-1 (ICAM-1) expression and inflammatory cytokine/chemoattractants, IL-6, CXCL8, and CCL5 production in vitro. BEAS-2B bronchial epithelial cells were incubated with 0.5-2 MOI (multiplicity of infection-infectious units/cell) of rhinovirus 16 (RV16). Then, 0.1-10 μM cilomilast or 10 nM dexamethasone, as inhibition control, were added pre- or post-1 h RV16 infection. Supernatant and cells were sampled at 8, 24, 48, and 72 h after infection. Cell surface ICAM-1 expression was detected by immunogold labelling and visualised by high-resolution scanning electron microscopy (HR-SEM), while IL-6, CXCL8, and CCL5 protein release and mRNA expression were measured using an ELISA and RT-PCR. Cilomilast significantly decreased RV16-induced ICAM-1 expression to approximately 45% ( < 0.01). CXCL8 protein/mRNA production was reduced by about 41% ( < 0.05), whereas IL-6 protein/mRNA production was increased to between 41-81% ( < 0.001). There was a trend to reduction by cilomilast of RV16-induced CCL5. Cilomilast has differential effects on RV16-induced ICAM-1 and interleukins, inhibiting virus-induced ICAM-1 expression and CXCL8 while increasing IL-6 production. These in vitro effects may help to explain the beneficial actions of this PDE4 inhibitor in vivo.