Interferon‐gamma (IFN‐γ) down‐regulates the rhinovirus‐induced expression of intercellular adhesion molecule‐1 (ICAM‐1) on human airway epithelial cells

Human rhinoviruses (HRV) are a major cause of upper respiratory tract infections in man, and can exacerbate existing pulmonary disease. The major group of HRV attach to ICAM- I, which is expressed on nasal and bronchial epithelial cells. To study the influence of biological mediators on ICAM-I expression, and consequently HRV attachment and infection, we compared the effects of various cytokines, alone and in combination, on ICAM-1 expression by an uninfected and HRV-infected bronchial epithelial cell line H292. Cytokines known to be released soon after viral infection, such as tumour necrosis factor-alpha (TNF-α), IL- Iβ and the chemokine IL-8 increase ICAM-1 expression on uninfected cells. Epithelial cells infected with live HRV-14 displayed marked up-regulation of ICAM- I compared with baseline. TNF-α further enhanced the HRV-induced increase in ICAM-I expression on epithelial cells, peaking at day 4 after infection, whilst IL-8 exhibited a steady increase in ICAM-I expression over 14 days. In contrast, IFN-y, a known Thl antiviral lymphokine, whilst increasing the level of ICAM-I on uninfected cells, induced a significant persistent down-regulation of ICAM-I expression on HRV-infected epithelial cells. With combinations of TNF-α and IFN-γ. ICAM-1 expression on HRV-infected cells was reduced to basal levels. The effects of IFN-γ were paralleled by a reduction in viral titres. Our in vitro model has provided useful insights into the early pathogenic events of HRV infection at the level of the host cell-virus interaction. Our data confirm that biological mediators play a crucial role in the pathogenesis as well as the course of HRV infection which is modulated by the types, and time kinetics of inflammatory cytokines in the immediate microenvironment.