Gold sodium thiomalate selectivity inhibits interleukin-5–mediated eosinophil survival,☆☆,

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Abstract

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 (106 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 × 10−9 to 2 × 10−5 mmol/L) and with GST (0.01 to 100 μmol/L) in 96-well, flat-bottomed microtiter plates at 37° 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. (J ALLERGY CLIN IMMUNOL 1995;96:251-6.)

Section snippets

Purification of eosinophils

Informed consent was obtained from all subjects participating in the following studies. Heparinized venous blood was obtained from patients with bronchial asthma (n = 18) with moderate eosinophilia (range, 6% to 15% eosinophils; median, 10%). Patients did not have symptoms and had not taken any medication at the time of the study. The granulocyte layer was isolated from the blood by centrifugation for 15 minutes at 1800 g on a Ficoll-Hypaque gradient (Nycomed Pharma AS, Oslo, Norway).

Influence of GST on IL-5–mediated eosinophil survival in vitro

To assess the effect of IL-5 on eosinophil survival, eosinophils were incubated in 10% FBS–RPMI 1640 with various concentrations of IL-5. We observed increased survival of eosinophils that was dependent on the dose of IL-5 and reached a plateau at a concentration of 2 × 10−6 mmol/L IL-5. When eosinophils were incubated for 72 hours in medium with IL-5 at concentrations ranging from 2 × 10−9 to 2 × 10−5 mmol/L or without IL-5, the viability was 48.3% ± 3.4%, 58.3% ± 5.4%, 72.3% ± 6.2%, 71.3% ±

DISCUSSION

IL-5 is considered to be the most important cytokine in the regulation of eosinophil function.8, 13 Among its various functions, IL-5 is known to prolong eosinophil survival by preventing programmed cell death, or apoptosis.22, 23, 24 In this study we showed that GST (concentrations of 0.01 to 100 μmol/L) inhibits IL-5–stimulated eosinophil survival without having a direct toxic effect on eosinophils. Moreover, when eosinophils were incubated for 72 hours with IL-5 (2 × 10−6 mmol/L) and GST (10

Acknowledgements

We thank Prof. Richard M. Silver, Medical University of South Carolina, for critical review of the manuscript. We are grateful to Ms. Kyoko Ohnuma and Ms. Kazuko Tokue for their technical assistance, and to Ms. Chiaki Watanabe and Ms. Yoshiko Saito for preparing the manuscript.

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    From the Department of Internal Medicine II, Fukushima Medical College.

    ☆☆

    Reprint requests: Shuzo Suzuki, MD, Division of Rheumatology and Immunology, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425-2229.

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