Nonsteroidal anti-inflammatory drug as tools for analysis of neutrophil functions

We investigated the effects of the nonsteroidal anti-inflammatory drugs diclofenac sodium, indomethacin and phenylbutazone on the activities relating to the migration and respiratory burst of polymorphonuclear leukocytes (PMN). When diclofenac sodium, was incorporated into the agarose gel at various concentrations below 100 micrograms/ml, it inhibited, in a dose-dependent fashion, spontaneous PMN migration and the directional migrations induced by both C5a-activated serum and peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). By contrast, phenylbutazone (below 100 micrograms/ml) only altered the directed PMN migration induced by FMLP, in two characteristic ways: by impairing the optimal response to 10(-7) M FMLP, and in particular, by restoring the loss of migration induced by higher but deactivating concentrations of 10(-6) and 10(-5) M. Indomethacin had similar effects to those of phenylbutazone on FMLP-induced PMN migration and in addition slightly impaired spontaneous PMN migration. The alterations in FMLP-induced migration caused by the three drugs tested were mainly chemokinetic and were due to changes in migratory speed. Of the three drugs, phenylbutazone and indomethacin also impaired FMLP-induced changes in the shape of PMN. All three interfered with the respiratory burst induced by FMLP but not with that induced by phorbol myristate acetate. These results demonstrate that phenylbutazone, indomethacin and diclofenac possess different spectra of biological activities as regards the parameters relating to PMN migration and respiratory burst, and therefore suggest that these drugs could serve as tools for investigating PMN functions.