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Alveolar macrophages from patients with beryllium disease and sarcoidosis express increased levels of mRNA for tumor necrosis factor-alpha and interleukin-6 but not interleukin-1 beta.

Abstract
Recent evidence suggests that the alveolar macrophage-derived cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) play important roles in granulomatous diseases. Our objective was to quantify the mRNA for these cytokines in beryllium disease, a human granulomatous disease of known etiology. We hypothesized that alveolar macrophages and bronchoalveolar lavage fluid from patients with beryllium disease and sarcoidosis would express increased levels of mRNA and proteins, respectively, for TNF-alpha, IL-1 beta, and IL-6 compared with those of normal individuals. We performed bronchoalveolar lavage and used a quantitative polymerase chain reaction to determine alveolar macrophage-derived cytokine gene expression. We determined lavage fluid cytokine levels by enzyme-linked immunosorbent assay. In patients with beryllium disease (n = 23), we observed elevated macrophage mRNA expression for TNF-alpha and IL-6 when compared with that of normal subjects (n = 7). Sarcoidosis patients (n = 6) also had increased expression for TNF-alpha and IL-6 compared with that of normal volunteers. IL-1 beta expression was similar in all three groups. In patients with beryllium disease (n = 39), lavage fluid TNF-alpha concentration was higher than that of 16 normal subjects. Lavage fluid IL-1 beta and IL-6 levels did not differ among the groups. This is the first report of macrophage cytokine expression in beryllium disease. These novel findings suggest that macrophage expression of TNF-alpha and IL-6 may be important in the human granulomatous inflammatory response.
AuthorsT W Bost, D W Riches, B Schumacher, P C Carré, T Z Khan, J A Martinez, L S Newman
JournalAmerican journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 10 Issue 5 Pg. 506-13 (May 1994) ISSN: 1044-1549 [Print] United States
PMID8179912 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Actins
  • DNA Primers
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
Topics
  • Actins (metabolism)
  • Adult
  • Aged
  • Base Sequence
  • Berylliosis (genetics, metabolism, pathology)
  • Bronchoalveolar Lavage Fluid (cytology)
  • DNA Primers
  • Female
  • Humans
  • Interleukin-1 (biosynthesis, genetics)
  • Interleukin-6 (biosynthesis, genetics)
  • Lung Diseases (genetics, metabolism, pathology)
  • Macrophages, Alveolar (metabolism)
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • RNA, Messenger (biosynthesis)
  • Sarcoidosis (genetics, metabolism, pathology)
  • Tumor Necrosis Factor-alpha (biosynthesis, genetics)

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