Phenotypic changes in neutrophils related to anti-inflammatory therapy

Previous work from the group has shown that non-steroidal anti-inflammatory agents given to volunteers and patients inhibit PMN function possibly by a ffecting the developing neutrophil during the differentiation process. In t his study indomethacin treatment in vivo reduced neutrophil chemotaxis and proteolytic degradation of fibronectin, with a maximal effect after 14 days . Stimulated neutrophil adherence to fibronectin was also reduced but this was not due to quantitative changes hi pr, integrin expression or function. L-Selectin expression on resting and stimulated neutrophils was increased after 14 days and there was a small decrease in plasma levers of soluble L- selectin. These effects, however, could not be reproduced by treatment of n eutrophils with indomethacin in vitro, suggesting they are due to effects o n differentiating/maturing PMNs. In an attempt to interpret these changes, studies were performed with dexamethasone, which is known to alter neutroph il function and kinetics. Dexamethasone treatment reduced chemotaxis and in creased superoxide generation after 1 day and was associated with increased expression of activated beta(2) integrins and reduced L-selectin expressio n on resting neutrophils. This suggests the appearance of mainly 'activated ' cells as a result of demargination and indicates that the effects of indo methacin are distinctive and not related to changes in compartmentalisation . (C) 2000 Elsevier Science B.V. All rights reserved.