Gold sodium thiomalate selectivity inhibits interleukin-5–mediated eosinophil survival☆,☆☆,★
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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2007, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :Gold has been shown to decrease neutrophil and macrophage phagocytosis and lymphocyte reactivity to antigen stimulation. 82 Gold inhibits eosinophil survival via IL-5 modulation. 83 Gold decreases prostaglandin and leukotriene production in vitro and inhibits IgE-mediated release of histamine from isolated basophils and lung mast cells. 84-87
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2000, Immunology and Allergy Clinics of North AmericaCitation Excerpt :The authors concluded that IL-5 characterizes a late-phase nasal reaction to allergen, and that even a single steroid dose can attenuate this response significantly. Interestingly, gold salts, which have been reported to be effective in the treatment of asthma, also have been shown to inhibit IL-5–mediated eosinophil survival.90 Because eosinophil apoptosis is an important mechanism in modulating allergic inflammatory responses and IL-5 is known to prolong eosinophil survival,47,107 these investigators surmised that gold sodium thiomalate (GST) blocks the IL-5–induced inhibition of eosinophil apoptosis, thereby providing its therapeutic effect.
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From the Department of Internal Medicine II, Fukushima Medical College.
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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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0091-6749/95 $3.00 + 0 1/1/63267