Inhibition of human basophil leukotriene release by antiinflammatory steroids

Robert P. Schleimer*, Deborah A. Davidson, Stephen P. Peters, Lawrence M. Lichtenstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

We have previously shown that 24-hour culture of human basophils with the antiinflammatory steroid dexamethasone produces an inhibition of the IgE-dependent release of histamine. In contrast, similar treatment of purified human lung mast cells does not inhibit the subsequent release of either histamine, prostaglandin D2, or leukotriene (LT) C4. We now show that incubation of mixed leukocytes for 24 h with 10-7M dexamethasone produces an inhibition of anti-IgE-induced basophil LTC4 release as detected by radioimmunoassay. In three experiments, control (CON) and dexamethasone (10-7M; DEX)-treated cells were challenged with 0.01, 0.03 and 0.1 μg/ml of anti-IgE, and histamine and LTC4 were monitored. LTC4 release (ng LTC4/μg total cell histamine) from cells stimulated with anti-IgE was: 0.01 μg/ml anti-IgE, 6.9 ± 4, 0.3 ± 0.1 (CON, DEX); 0.03 μg/ml anti-IgE, 13.8 ± 4.7, 0.9 ± 0.5; 0.1 μg/ml anti-IgE, 19.5 ± 2.3, 4.9 ± 1.2. Histamine release was inhibited by 50-75% by treatment with DEX in these experiments. Dose-response studies (n = 4) indicate that the inhibitory actions of DEX on LTC4 release occur in the range of 10-10 to 10-7M. The concentration of DEX at which LTC4 release was inhibited by 50% (IC50) was approximately 2 × 10-9M. Another glucocorticoid (betamethasone) inhibited LTC4 release, while the nonglucocorticoids tetrahydrocortisone and β-estradiol were inactive. High performance liquid chromatography (HPLC) analysis (coupled with RIA) indicated that the relative proportions of LTC4, LTD4, and LTE4 did not differ in supernatants from CON- and DEX-treated, anti-IgE-challenged cells. This suggests that DEX does not reduce immunoactive LTC4 by increasing its metabolism to LTD4 and LTE4. Since basophil-derived sulfidopeptide leukotrienes may play an important role in inflammatory diseases, the inhibition of basophil leukotriene release by steroids may be a significant part of their antiinflammatory action.

Original languageEnglish (US)
Pages (from-to)241-243
Number of pages3
JournalInternational archives of allergy and immunology
Volume77
Issue number1-2
DOIs
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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