THE EFFECTS OF SOME ANTIRHEUMATIC DRUGS ON AN in vitro MODEL OF HUMAN POLYMORPHONUCLEAR LEUCOCYTE CHEMOKINESIS

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Abstract
1 A rapid, reproducible in vitro assay for studying the chemokinetic movement of human polymorphonuclear leucocytes (PMNs) is described. Two synthetic peptides, formyl methionyl-leucylphenylalanine (FMLP) and formyl methionyl-phenylalanine (FMP), were used as standard chemokinesins. 2 Maximal chemokinetic movement was observed with peptide concentrations of 2.5 nm (FMLP) and 100 μm (FMP). EC50 values of 650.0 ± 60.0 pm and 27.0 ± 3.5 μm respectively are similar to those reported for chemotactic activity of the peptides in micropore filter assays. 3 The PMN chemokinetic response to FMLP was enhanced by histamine (100 nm) and vitamin C (2.5 μm). 4 Human serum albumin was shown to induce chemokinesis but to antagonize the response to FMLP in a dose-related fashion. Fibrinogen similarly antagonized the cell response to peptide. 5 Levamisole (250 nm to 2.5 μm) significantly potentiated the chemokinetic responses to FMLP and FMP in a dose-related manner. The chemokinetic response to FMLP was unaffected by d-penicillamine (250 μm to 10 mm) while alclofenac (500 μm to 1 mm), salicylic acid (250 μm to 10 mm) and indomethacin (100 μm to 1 mm) caused dose-related inhibition.