EFFECT OF FLUTICASONE PROPIONATE ON NEUTROPHIL CHEMOTAXIS, SUPEROXIDEGENERATION, AND EXTRACELLULAR PROTEOLYTIC ACTIVITY IN-VITRO

Background - Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil fun ction is uncertain. Fluticasone propionate is a new topically active s ynthetic steroid which can be measured in body fluids and which underg oes first pass metabolism. Methods - The effects of fluticasone propio nate on the function of neutrophils isolated from normal, healthy cont rol subjects and on the chemotactic activity of sputum sol phase were assessed. Results - Preincubation of neutrophils with fluticasone prop ionate reduced the chemotactic response to 10(-8) mol/1 F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent m anner. Furthermore, when fluticasone propionate was added to sputum fr om eight patients with stable chronic obstructive bronchitis the chemo tactic activity of a 1:5 dilution of the sol phase fell from a mean (S E) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 1 1.9 (0.6) cells field at 1 mu mol/1, 10 mu mol/1, and 100 mu mol/1, re spectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells a nd by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1 % inhibition of stimulated cells with 1 mu mol/1 fluticasone propionat e, 24% and 18.7% inhibition respectively at 100 mu mol/1 fluticasone p ropionate. Fluticasone propionate had no effect on generation of super oxide anion by resting or stimulated cells. Conclusions - These result s indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connecti ve tissue.