Alteration of chloroquine accumulation in human polymorphonuclear leucocytes under inflammatory conditions

The present study concerns the established antirheumatic drug chloroquine (CQ) in relation to a possible target for drug therapy, the polymorphonuclear leucocyte (PMN). Its primary aim was to find out whether inflammatory conditions would influence the cell association of CQ. After a suitable ligand-binding assay was developed to measure the cellular association of CQ, the normal characteristics of the cellular transport of CQ were determined. The effect of the inflammatory conditions on CQ cell association was investigated with peripheral PMNs from rheumatoid arthritis (RA) patients, and with normal PMNs, in the absence and presence of the soluble cell-stimulators phorbol ester and chemotactic peptide. Under inflammatory conditions the intracellular concentration of CQ is reduced. This decrease is explained by three possibilities which are involved in cell activation: the leucocyte volume expansion, the cytoplasmic or lysosomal pH changes, and the exocytic release of the granules (degranulation). Our results suggest that this decrease will adversely affect the therapeutic effects, if the mode of anti-inflammatory action of CQ is related to the intracellular drug concentrations.