Abstract
Background: Cytokine imbalance and cellular migration to inflammatory sites are critical components of allergic diseases. The purpose of this investigation was to study the in vitro effect of montelukast on cytokine secretion and migration of activated T cells, as well as production of pro-inflammatory cytokines by macrophages.
Methods: Peripheral T cells obtained from healthy volunteers were cultured in wells coated with the combination of anti-CD3 monoclonal antibody (mAb) and anti-CD26 mAb, anti-CD28 mAb, or anti-CD3 mAb with PMA, in the presence or absence of montelukast. T cell proliferation and the production of cytokines were measured by [3H]thymidine incorporation assay and ELISA, respectively. In addition, transendothelial migration of T cells and production of pro-inflammatory cytokines by macrophages were examined.
Results: Montelukast inhibited T cell proliferation and the production of IL-4, IL-5, IL-6, and TNF-alpha by T cells under each co-stimulatory condition tested, whereas it exhibited no effect on the production of IL-2 or IFN-gamma. In addition, T cell migration and the production of such pro-inflammatory cytokines as TNF-alpha and IL-6 by macrophages were inhibited by montelukast.
Conclusion: These results indicate that montelukast has a specific inhibitory effect on Th2-type cytokine production. Moreover, montelukast inhibited T cell migration and pro-inflammatory cytokine production by T cells and macrophages, suggesting that montelukast might be useful for the treatment of T cell-mediated allergic inflammatory disorders, including asthma.