Benzydamine inhibits monocyte migration and MAPK activation induced by chemotactic agonists.

1 The present study was aimed to investigate the effect of benzydamine, an anti-inflammatory drug devoid of activity on arachidonic acid metabolism, on monocyte chemotaxis and to define the possible biochemical correlates of activity. 2 Benzydamine inhibited monocyte chemotaxis in response to three classes of chemoattractants: the prototypic CC-chemokine CCL2 (MCP-1), the microbial product fMLP and the complement cascade component C5a. The effect was dose-dependent with IC50's of 100, 50 and 45 muM for MCP-1/CCL2, fMLP and C5a, respectively. At the dose of 100 muM, the effect resulted in a 50+/-10% inhibition of MCP-1/CCL2-induced chemotaxis and 53+/-6 and 54+/-5% inhibitions of chemotaxis in response of fMLP and C5a, respectively (n=3). 3 Receptor expression as well as calcium fluxes in response to chemoattractants were not affected by benzydamine. 4 Benzydamine strongly inhibited chemoattractant-induced activation of the mitogen-activated protein kinase (MAPK) ERK1/2, and of its upstream activator kinase MEK1/2. ERK1/12 activation in response to chemoattractants was 89-98% inhibited by a 100 muM concentration of benzydamine with an IC50 of 30 muM. 5 Under the same experimental conditions, pretreatment with 100 muM benzydamine caused a 75-89% inhibition of p38 activation (IC50 25 muM). 6 These results indicate that the anti-inflammatory activity of benzydamine is exerted at multiple levels, including monocyte migration to chemotactic factors associated to a blockage of ERK and p38 MAPK pathways.