Gold sodium thiomalate selectivity inhibits interleukin-5-mediated eosinophil survival.
Gold sodium thiomalate (GST) has been used for treatment of patients with bronchial asthma. In this study we investigated the effects of GST on interleukin (IL)-5-mediated eosinophil survival in vitro. Blood cells were obtained from patients with bronchial asthma (n = 18). Eosinophils were purified from the blood samples by a Percoll discontinuous method and negative selection of neutrophils. Eosinophils (10(6) cells/ml) were incubated for 96 hours in 10% fetal bovine serum-RPMI 1640 (Nissui Pharmaceutical Co. Ltd., Tokyo, Japan) with various concentrations of recombinant human IL-5 (2 x 10(-9) to 2 x 10(-5) mmol/L) and with GST (0.01 to 100 mumol/L) in 96-well, flat-bottomed microtiter plates at 37 degrees C in a humidified 5% carbon dioxide atmosphere. Eosinophil viability was determined by trypan blue exclusion. IL-5 enhanced eosinophil survival in a dose-dependent manner. Higher concentrations of GST inhibited IL-5-mediated eosinophil survival. Moreover, GST induced apoptosis of eosinophils by antagonizing the effects of IL-5. However, GST did not inhibit IL-3- or granulocyte-macrophage colony stimulating factor-mediated eosinophil survival, suggesting that GST selectivity inhibits IL-5-mediated eosinophil survival. These results suggest that IL-5-mediated eosinophil survival is inhibited by GST and that GST blocks eosinophil apoptosis by IL-5. It is possible that GST may be capable of controlling eosinophil functions regulated by IL-5 in patients with bronchial asthma.
Suzuki
S
S
Department of Internal Medicine II, Fukushima Medical College.
Okubo
M
M
Kaise
S
S
Ohara
M
M
Kasukawa
R
R
D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000097:blood; D004247:DNA / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects*; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*
D015848:Interleukin-5; D006052:Gold Sodium Thiomalate; D004247:DNA