Interleukin-8 plays a significant role in IgE-mediated lung inflammation

Abstract

Interleukin (IL)-8 is a potentially important cytokine in allergic respiratory responses since it is released by many resident lung cells, and it is a potent granulocyte chemoattractant. Therefore, we induced an immunoglobulin (Ig)E-mediated response in human lung samples and studied whether IL-8 was produced in sufficient quantities to promote human neutrophil and eosinophil migration across naked filters and endothelial and pulmonary epithelial monolayers cultured on these filters. Fresh human lung fragments from 16 thoracotomy specimens were treated with either a 1:100 dilution of anti-IgE or buffer (control) for 30 min. All anti-IgE treated lung samples had significant release of histamine and neutrophil and eosinophil chemotactic activity. Fourteen of the 16 lung samples had a significant increase in IL-8 subsequent to anti-IgE treatment (p<0.01). Anti-IL-8 antibody (4 microg x mL[-1]) inhibited 42% and 53% of neutrophil and eosinophil chemotactic activity respectively, contained in supernatants from anti-IgE-treated lung samples. Finally, we found that IL-8 at a concentration near that measured after anti-IgE treatment of lung samples (2,000 pg x mL[-1]) induced neutrophil and eosinophil migration through naked filters and endothelial and pulmonary epithelial cell monolayers. Thus, human lung IgE-mediated responses in vitro results in the rapid release of interleukin-8 in amounts sufficient to affect a biological response, granulocyte transcellular migration, indicating that interleukin-8 may play a significant role in allergic respiratory diseases.