lasalocid and Arthritis--Rheumatoid

The effects of auranofin on the function of neutrophil polymorphonuclear granulocytes (PMN) have been studied in vitro and in vivo. Preincubation of human PMN with auranofin (1-4 micrograms/ml) increased their adherence to nylon fibres and f-met-leu-phe-(fMLP) induced aggregation. PMN migration, phagocytosis, bactericidal capacity and phagocytosis-associated enzyme release were all significantly inhibited by auranofin in a dose-dependent way. Enzyme release stimulated by f-MLP, chemoluminescence and the release of superoxide anions all showed a biphasic response to preincubation with auranofin. They showed an increase at low concentrations and inhibition at high concentrations. In studies of 3H-fMLP binding auranofin did not affect receptor numbers but increased binding affinity. Auranofin at higher concentrations decreased phorbolmyristate acetate and fMLP induced changes in surface charge and membrane potential. In vivo, auranofin administered to rats, did not prevent either the neutropenia induced by zymosan-activated serum or the corresponding rise in plasma lactoferrin levels. PMNs from six rheumatoid arthritis patients treated with auranofin (6 mg/day) for 23 weeks showed changes in bactericidal activity, chemotaxis and chemiluminescence independent of the clinical response. Enzyme release, however, was reduced in PMNs from clinical responders and showed no change in non-responders.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Cell Aggregation; Glucuronidase; Gold; Humans; In Vitro Techniques; Kinetics; Lasalocid; Muramidase; Neutrophils; Phagocytosis; Rats

The synthesis of products of the 5-lipoxygenase pathway by synovial fluid (SF) and peripheral blood neutrophils of 12 patients with rheumatoid arthritis was compared in 3 experimental conditions using high performance liquid chromatographic analysis. Major differences were observed when blood and SF neutrophils were incubated with ionophore A23187, the formation of all 5-lipoxygenase products being lower (p less than 0.0005) in the SF neutrophils. Addition of exogenous arachidonic acid to the A23187 stimulated cells partially overcame the difference in 5-lipoxygenase product synthesis between the 2 neutrophil populations. In contrast, upon incubation with arachidonic acid alone, SF neutrophils produced significantly larger amounts of 5-lipoxygenase products. The increased reactivity of the SF neutrophil 5-lipoxygenase to arachidonic acid and the decreased 5-lipoxygenase product synthesis upon A23187 stimulation may be the consequence of the previous activation of the cells and 5-lipoxygenase product synthesis in situ.

Topics: Adult; Aged; Arachidonic Acids; Arthritis, Rheumatoid; Cells, Cultured; Chromatography, High Pressure Liquid; Female; Humans; Lasalocid; Leukotriene A4; Leukotriene B4; Leukotrienes; Male; Middle Aged; Neutrophils; SRS-A; Synovial Fluid