Antiinflammatory steroids inhibit granulocyte/macrophage colony-stimulating factor production by human lung tissue

M. Kato*, R. P. Schleimer

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Granulocyte/macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor which has been shown to induce proliferation and activation of inflammatory cells, and may play a role in allergic diseases and experimental allergic reactions. Since little is known about the involvement of cytokines in allergic inflammation in the lung, we investigated whether human lung fragments produce GM-CSF in vitro. The present studies demonstrate that human lung fragments produce GM-CSF in vitro and that glucocorticoids are potent inhibitors of this cytokine production. Human lung was cut into fragments, rinsed, and cultured in 60-mm tissue culture plates containing 50 mg of tissue in RPMI 1640 with antibiotics in the presence or absence of a variety of steroids for 18 h. Lung fragments were rinsed and then incubated for an additional 4 h. Supernatants were harvested and analyzed for GM-CSF activity using the GM-CSF/interleukin (IL)-3 responsive M-07e human luekemic cell line. Steroids alone had no effect on M-07e proliferation. Human lung fragments produced 32.1 ± 11.8 ng of GM-CSF equivalents per gram wet weight of tissue during the 4 h incubation (mean ± S.E.M., n = 5, range 9.2-74.2). While specific antisera against human GM-CSF neutralized 96.8 ± 2.8% (n = 5) of the activity, anti-IL-3 antibody had no effect, suggesting most or all of this activity was GM-CSF. Treatment of lung fragments in vitro for 18 h with hydrocortisone (HC) inhibited the production of GM-CSF dose-dependently. Maximal inhibition of GM-CSF production was 72.8 ± 4.0% at a concentration of 10-6m hydrocortisone (n = 5), and the molar concentration of HC that inhibited of GM-CSF production by lung tissue by 50% (IC50) was approximately 4.5 × 10-7m. Kinetic studies revealed that a 6 h preincubation with the drug was required for 50% inhibition of GM-CSF production. HC and other glucocorticoids, at a concentration of 0.1 μm, demonstrated significant inhibition of GM-CSF release. Based on the rank order of potency of several glucocorticoids, and the fact that nonglucocorticoid steroids including testosterone and β-estradiol (0.1 μm) had no effect, we suggest that this is a specific receptor-mediated effect. We conclude that human lung produces GM-CSF in vitro and that antiinflammatory steroids are potent and effective inhibitors of the production of this cytokine. This may contribute to the therapeutic efficacy of these drugs in pulmonary diseases.

Original languageEnglish (US)
Pages (from-to)113-124
Number of pages12
JournalLung
Volume172
Issue number2
DOIs
StatePublished - Mar 1 1994

Keywords

  • Glucocorticoids
  • Granulocyte/macrophage colony-stimulating factor
  • Lung

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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