Interleukin 1 production by human lung tissue. II. Inhibition by anti-inflammatory steroids

B. S. Bochner, B. K. Rutledge, R. P. Schleimer

Research output: Contribution to journalArticlepeer-review

Abstract

Glucocorticoids block the localized accumulation of leukocytes as sites of inflammation by preventing their adherence to vascular endothelium. This implies that glucocorticoids are acting either on the leukocytes, endothelium, or cells which produce adherence-promoting factors (such as interleukin 1 (IL-1)). Previous studies have shown that dexamethasone (DEX) treatment of either polymorphonuclear leukocytes (PMN) or human umbilical vein vascular endothelial cells (VEC) or both in vitro does not prevent adherence induced by thrombin or formyl-methionyl-leucyl-phenylalanine (f-met peptide). We now show that pretreatment of PMN and/or VEC for 24 hr with 0.1 μM DEX had no effect on adherence of PMN to VEC activated with IL-1 (2 U/ml), lipopolysaccharide (1 μg/ml), or 12-O-tetradecanoylphorbol-13-acetate (30 ng/ml) suggesting that glucocorticoids may inhibit adherence in vivo by blocking formation of IL-1 and other adherence-inducing stimuli. We have recently established that cultured human lung fragments produce IL-1 in vitro. To investigate whether glucocorticoids could inhibit the production of adherence-inducing factors, we examined the effect of glucocorticoids on IL-1 production from human lung tissue. Treatment of human lung fragments in vitro for 18 hr with glucocorticoids such as DEX and hydrocortisone resulted in dose dependent inhibition of IL-1 production; these and other glucocorticoids, at concentrations ranging between 0.1 and 1 μM, produced greater than 50% inhibition of IL-1 release. Nonglucocorticoid steroids including testosterone and β-estradiol (1 μM) had no effect. Inhibition of IL-1 production occurred after a lag period of 5 to 16 hr, and the relative glucocorticoid potencies agreed with their known anti-inflammatory potencies in vivo (beta-methasone ≃ triamcinolone acetonide > DEX > fludrocortisone > prednisolone > hydrocortisone). Inhibition of IL-1 production in vivo may, in part, explain the remarkable ability of glucocorticoids to prevent the adherence of leukocytes to endothelium and their accumulation at an inflammatory site.

Original languageEnglish (US)
Pages (from-to)2303-2307
Number of pages5
JournalJournal of Immunology
Volume139
Issue number7
StatePublished - 1987

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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