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Abstract
Diclofenac sodium, a non steroidal anti-inflammatory agent, was studied for its influence
on the locomotion of human polymorphonuclear neutrophils (PMN), in an attempt to define
the mechanism governing the drug's anti-inflammatory properties. PMN locomotion was
measured by the agarose technique under two conditions of stimulation of cell migration:
in the presence of a gradient of stimuli (chemotaxis) and in the presence of various
amounts of stimuli incorporated in the gel (chemokinesis). At concentrations below
10 micrograms/ml, diclofenac in the gel reduced, in a dose-dependent manner, the directed
locomotion of PMN induced by a gradient of C5a-activated serum, peptide N-formyl-methionyl-leucyl-phenylalanine
(FMLP) or Klebsiella pneumoniae culture supernatant (KPCS). Diclofenac also inhibited
the random locomotion of unstimulated PMN, as well as the PMN chemokinetic activity
induced by various amounts of FMLP or activated serum. Inhibition of PMN locomotion
by diclofenac decreased when the concentration of the stimulant was raised; this inhibition
was inversely related to the concentration of heat-inactivated fetal calf serum in
the medium. The directed locomotion and chemokinesis of PMN, induced by FMLP were
also reduced in PMN preincubated with diclofenac before migration, suggesting a direct
cellular effect of diclofenac. On the other hand, diclofenac did not affect the changes
in shape induced in floating PMN by FMLP or activated serum. The observation that
diclofenac did not alter the ingestion rate of bacteria by PMN indicates that this
drug is not cytotoxic for PMN. Consequently, diclofenac reduces PMN locomotion by
interfering with the PMN chemokinetic activity. Diclofenac is an anti-inflammatory
drug possessing the original property of acting as a negative chemokinetic agent,
for migration of both stimulated and unstimulated PMN. It should therefore be a useful
tool for analyzing the elements controlling PMN locomotion speed.