Interleukin-1-beta Gene Expression in Human Monocytes and Alveolar Macrophages from Normal Subjects and Patients with Sarcoidosis

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Abstract
To assess the ability of human alveolar macrophages to produce interleukin-1-beta (IL-1-beta), we examined IL1-beta mRNA accumulation in autologous monocytes and alveolar macrophages from normal volunteers. Escherichia coli lipopolysaccharide stimulation of monocytes induced rapid IL1-beta mRNa accumulation, reaching a maximum at 2 to 4 h and declining thereafter. Alveolar macrophages, however, accumulated much less mRNA than did monocytes. This difference could not be explained by differences in kinetics of IL1-beta gene expression between the 2 cell types, isolation techniques, or alveolar macrophage lidocaine exposure. This suggests that differences in transcription of the IL1-beta gene exist between these 2 cell types. Aging is a possible factor important in some functional differences between these 2 cell types. To determine if this difference in the capacity to express the IL1-beta gene might be a function of cell maturity, monocytes were aged in vitro for 7 days. After this culture period, monocytes had a marked decrease in the ability to accumulate IL1-beta mRNA, suggesting that cell aging may be one mechanism involved in producing these transcriptional differences. Because IL1-beta has also been implicated in the inflammatory and fibrotic responses in pulmonary sarcoidosis, 4 patients with newly diagnosed sarcoidosis underwent bronchoalveolar lavage, and IL1-beta mRNA accumulation was compared in their alveolar macrophages and blood monocytes. Comparing normal alveolar macrophages to those from patients with sarcoidosis showed no differences in the kinetics of IL1-beta mRNA expression or in the LPS-induced levels of IL1-beta mRNA accumulation. In addition, augmented levels of IL1-beta transcript were noted in unstimulated sarcoid alveolar macrophages.