Effects of auranofin on leukotriene production and leukotriene stimulated neutrophil function

Arachidonic acid is metabolized in neutrophils by lipoxygenase to leukotrienes, which are suggested to play a central role in inflammation. The antirheumatic drug auranofin (4 g/ml) was found not to inhibit neutrophil production of the lipoxygenase products 5-HETE, 15-HETE and LTB₄,in vitro when stimulated with the calcium ionophore A23187. Auranofin, however, modulated neutrophil aggregation, enzyme release and chemotaxis induced by LTB₄. The results suggest that auranofin may exert some of its antirheumatic effects through affecting neutrophil responses to leukotrienes.Supported by grants from: Swedish National association against Rheumatism, King Gustav V 80 years Fund, Tore Nilssons Fund, P and A Hedlunds Fund, Swedish Society for Medical Research, Förenade Liv Mutual Group Life Insurance Company, Stockholm, Sweden.