title: Beryllium-stimulated release of tumor necrosis factor-alpha, interleukin-6, and their soluble receptors in chronic beryllium disease.
abstract: Chronic beryllium disease (CBD) provides a model system in which to evaluate the antigen-stimulated, cell-mediated, immune response that leads to granulomatous lung disease. We hypothesized that beryllium salts would stimulate bronchoalveolar lavage (BAL) cell release of tumor necrosis factor-alpha (TNF-alpha) and lnterleukin-6 (IL-6), and their soluble receptors, soluble TNF receptor I (sTNF RI), sTNF RII, and sIL-6R and that chronic exposure to antigen would increase production of soluble receptors in the serum and BAL fluid (BALF) of beryllium-sensitized and CBD patients. We have demonstrated (1) similar constitutive TNF-alpha, IL-6, and soluble receptor production by control subjects and CBD patients, (2) a BeSO4-stimulated increase in TNF-alpha and IL-6 production by CBD-derived BAL cells, and (3) a BeSO4-induced decrease in sTNF RII production by BAL cells from control subjects. We measured increased serum sTNF RI and serum and BALF sIL-6R in beryllium-sensitized subjects and increased sTNF RI and RII in serum and sIL-6R and sTNF RII and BALF in CBD patients. These changes correlated with pulmonary lymphocytosis and clinical measures of disease severity, indicating that soluble receptors may reflect disease status.
authors.affiliation: National Jewish Medical and Research Center, Division of Environmental and Occupational Health Sciences, Denver, Colorado, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Tinkle
authors.forename: L S
authors.initials: LS
authors.lastname: Newman
mesh_terms: D000328:Adult; D001607:Berylliosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001608:Beryllium / Q000009:adverse effects / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002908:Chronic Disease; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011659:Pulmonary Gas Exchange; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014797:Vital Capacity
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C020711:beryllium sulfate; D001608:Beryllium