Effect of non-steroidal anti-inflammatory drugs on neutrophil chemotaxis--an in vitro and in vivo study.

We have studied the effects of the two non-steroidal anti-inflammatory drugs (NSAIDs), nabumetone and indomethacin, on neutrophil chemotaxis in vitro and in vivo. When used in therapeutic concentrations in vitro, neither agent had any effect on the chemotactic response of neutrophils isolated from healthy volunteers. This was true for the three chemotactic agents studied: FMLP, zymosan activated serum and purulent sputum. Nabumetone and indomethacin decreased neutrophil chemotaxis over a period of 2 weeks in 12 normal subjects in vivo. The average chemotactic response to 10(-8) mol/l FMLP for all 12 during the control period was 42.1 +/- 6.1 cells per high power field and this fell to 26.1 +/- 4.9 (P less than 0.025) after 7 days and to 15.6 +/- 2.5 (P less than 0.005) after 14 days. The results were similar for both drugs analysed independently. The results suggest that NSAIDs have no effect on the chemotactic response of mature cells in vitro, but suppress chemotaxis progressively when given in vivo. This may be explained by an effect of NSAIDs on maturing cells prior to release into the circulation.