IL-4 induces ICAM-1 expression in human bronchial epithelial cells and potentiates TNF-alpha

Interleukin (IL)-4 is thought to contribute to the Th2 type of immune respo nse and hence the development of allergic reactions such as asthma. In asth matic patients, the airway epithelium expresses increased amounts of the ce ll surface adhesion molecule intercellular adhesion molecule (ICAM)-1 (CD54 ). One cytokine capable of inducing ICAM-1 in airway epithelial cells, tumo r necrosis factor-alpha (TNF-alpha), is present in asthma. This study evalu ated if IL-4 either alone or together with TNF-alpha costimulation might mo dulate CD54 expression by human bronchial epithelial cells (HBECs). CD54 po sitivity increased in response to IL-4 (16 +/- 2% positive vs. 3 +/- 1%, P < 0.01); greater induction of CD54 resulted from TNF-alpha (45 +/- 2%, P < 0.001). Costimulation with TNF-alpha plus IL-4 further augmented expression (56 +/- 1%, P < 0.05). Immunoperoxidase results were confirmed by flow cyt ometry. RT-PCR revealed no increase in ICAM-1 mRNA expression under control conditions or after stimulation with IL-4 alone. TNF-alpha increased IL-4 mRNA, and IL-4 potentiated this. Functionally, IL-4 augmented the adhesion of THP-1 monocyte/macrophage cells to monolayers of HBECs both alone and in the presence of TNF-alpha. We conclude that 1) IL-4 augments epithelial ce ll ICAM-1 expression, 2) IL-4 potentiates the adhesion of THP-1 monocyte/ma crophage cells to epithelial cells, and 3) modulation of epithelial cell IC AM-1 expression by IL-4 may play a role in the immunopathology of bronchial asthma.