INTERFERON-GAMMA (IFN-GAMMA) DOWN-REGULATES THE RHINOVIRUS-INDUCED EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) ON HUMAN AIRWAYEPITHELIAL-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-1, which is expressed on nasal and b ronchial epithelial cells. To study the influence of biological mediat ors on ICAM-1 expression, and consequently HRV attachment and infectio n, we compared the effects of various cytokines, alone and in combinat ion, on ICAM-1 expression by an uninfected and HRV-infected bronchial epithelial cell line H292. Cytokines known to be released soon after v iral infection, such as tumour necrosis factor-alpha (TNF-alpha), IL-1 beta 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-1 compared with baseline. TNF-alpha further enhance d the HRV-induced increase in ICAM-1 expression an epithelial cells, p eaking at day 4 after infection, whilst IL-8 exhibited a steady increa se in ICAM-1 expression over 14 days. In contrast, IFN-gamma, a known Th1 antiviral lymphokine, whilst increasing the level of ICAM-1 on uni nfected cells, induced a significant persistent down-regulation of ICA M-1 expression on HRV-infected epithelial cells. With combinations of TNF-alpha and IFN-gamma, ICAM-1 expression on HRV-infected cells was r educed to basal levels. The effects of IFN-gamma were paralleled by a reduction in viral titres. Our in vitro model has provided useful insi ghts into the early pathogenic events of HRV infection at the level of the host cell-virus interaction. Our data confirm that biological med iators play a crucial role in the pathogenesis as well as the course o f HRV infection which is modulated by the types, and time kinetics of inflammatory cytokines in the immediate microenvironment.