Detection of alveolar macrophage-derived IL-1 beta in asthma. Inhibition with corticosteroids

J Immunol. 1992 Nov 1;149(9):3078-82.

Abstract

This study investigated alveolar macrophage function in asthma as assessed by the presence and source of the cytokine IL-1 beta. Bronchoalveolar lavage (BAL) fluid and cell pellets were obtained at 4 a.m. from a cohort of asthmatic subjects. Normal subjects were used as controls. Asthmatic BAL fluid contained 57.0 +/- 5.9 pg/ml of IL-1 beta as determined by ELISA. No IL-1 beta could be identified in the BAL fluid of the control group. This IL-1 represented synthesis by cells of the airway as assessed by the presence of IL-1 beta-specific mRNA transcripts in the BAL cell pellets. Inasmuch as IL-1 beta transcripts are known to be present for only a short time period after activation (approximately 0.5 to 16 h), the presence of transcripts represents recent cellular activation. Using the technique of in situ hybridization, IL-1 beta transcripts were found to be located exclusively within alveolar macrophages, and a mean of 40 +/- 14% of alveolar macrophage were activated at the time of the lavage. Corticosteroids are known to be efficacious in the treatment of asthma. Administration of a single 50-mg dose of prednisone at 3 p.m. resulted in diminished IL-1 beta protein concentration in the BAL fluid (28.3 +/- 5.7 pg/ml; p < 0.01 compared to baseline) and completely abrogated IL-1 beta mRNA expression. In summary, these studies demonstrate that IL-1 beta is synthesized within the airways by alveolar macrophage and suggest that IL-1 beta may be a mediator of asthma. Inhibition of IL-1 beta may be an additional mechanism for the efficacy of corticosteroids in the treatment of asthma.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Asthma / drug therapy
  • Asthma / immunology*
  • Asthma / pathology
  • Base Sequence
  • Bronchoalveolar Lavage Fluid / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • In Situ Hybridization
  • Interleukin-1 / biosynthesis*
  • Macrophage Activation / immunology
  • Macrophages, Alveolar / immunology*
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Polymerase Chain Reaction
  • Prednisone / pharmacology
  • RNA, Messenger / analysis
  • Transcription, Genetic

Substances

  • Interleukin-1
  • Oligonucleotide Probes
  • RNA, Messenger
  • Prednisone