A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity.

• DOI: 10.4049/jimmunol.157.6.2654
• Publication Date: 2022-12-31T12:42:34Z
• Authors: J D Spahn; S J Szefler; W Surs; D E Doherty; S R Nimmagadda; D Y Leung
• Keywords: Monocyte

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