A Novel Action of IL-13: Induction of Diminished Monocyte Glucocorticoid Receptor-Binding Affinity

Joseph D. Spahn, Stanley J. Szefler, Wendy Surs, Dennis E. Doherty, Sai R. Nimmagadda, Donald Y.M. Leung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

We have recently demonstrated that the combination of IL-2 and IL-4 blunts T cell responses to glucocorticoids in steroid resistant (SR) asthma by reducing glucocorticoid receptor (GCR)-binding affinity. Since immune activation appears to be involved in the acquisition of steroid resistance, we sought to identify whether other cytokines could also induce diminished GCR-binding affinity. In the current report, utilizing a [3H]dexamethasone radioligand-binding assay and Scatchard analysis, we found that IL-13, a cytokine with similar actions as IL-4, could induce diminished GCR binding-affinity (GCR Kd = 34.4 ± 2.3 nM with IL-13 vs Kd = 8.8 ± 0.7 nM for unstimulated control cells; p < 0.001) in PBMC from normal subjects. In contrast, PBMC incubated with IL-1, IL-3, IL-5, IL-7, IL-8, IL-12, or granulocyte-macrophage-CSF had no effect on GCR-binding affinity; and no additive effect to the decreased GCR-binding affinity was noted when IL-13 was cocultured with IL-2 or IL-4. The cell target of IL-13-induced GCR effects was studied and found to reside in the non-T cell population; specifically, the monocyte fraction. To determine the functional significance of the decreased GCR-binding affinity, monocytes were pretreated with and without IL-13 prior to stimulation with LPS and hydrocortisone. IL-13 pretreatment of monocytes significantly diminished (p = 0.005) the suppressive effects of hydrocortisone on LPS-induced IL-6 production. IL-13, by virtue of its ability to induce diminished GCR-binding affinity, may contribute to impaired GC responsiveness during inflammatory illnesses.

Original languageEnglish (US)
Pages (from-to)2654-2659
Number of pages6
JournalJournal of Immunology
Volume157
Issue number6
StatePublished - Sep 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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