Effects of anti-inflammatory drugs on polymorphonuclear leukocyte aggregation (Abstract)

Abstract

Rat peritoneal leukocytes (84 ±4% neutrophils) have been shown to aggregate in vitro after addition of zymosan activated plasma (ZAP) or formyl-methionyl-leucyl-phenylalanine (FMLP). Aggregation, caused by high circulating levels of activated complement products, plays a role in the transient neutropenia associated with certain clinical conditions and the effects of some anti-inflammatory drugs on FMLP and ZAP induced aggregation have therefore been examined. PMN suspensions (0.5 ml of 1 × 10⁷ cells ml^-1) were stirred at 900 rev/min for 5 min at 37 °C in a Payton aggregometer, an aliquot of drug was then added to the cuvette 1 min prior to the addition of either 5 × 10^-7 mol/1 FMLP or 2% ZAP. Aggregation was measured as a change in optical density and results expressed as the percentage reduction of the response in the presence of the drug compared to that observed with vehicle alone. Methyl prednisolone (0.03–2mg ml^-1), hydrocortisone sodium succinate (0.1–4mg ml^-1) and colchicine (10^-5-10^-3 mol/1) caused a dose related reduction in the aggregation response to both FMLP and ZAP. Indomethacin (10^-6-10^-4 mol/1) and aspirin (2.5 × 10^-3 mol/1) significantly reduced the aggregation response to FMLP without altering the response to ZAP. The mechanism of these effects may involve blockade of the receptor sites on the PMN to the aggregating agents and inhibitory activity on pathways of arachidonic acid metabolism.