Detection of alveolar macrophage-derived IL-1 beta in asthma. Inhibition with corticosteroids.
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.
Borish
L
L
Department of Medicine, University of Colorado Health Sciences Center, Denver 80206.
Mascali
J J
JJ
Dishuck
J
J
Beam
W R
WR
Martin
R J
RJ
Rosenwasser
L J
LJ
D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000096:biosynthesis*; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic
D007375:Interleukin-1; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011241:Prednisone