IL-4 Fails to Regulate In Vitro Beryllium-Induced Cytokines in Berylliosis

Details

• Personal Author:
  Balkissoon R ; Barker EA ; Kittle LA ; Maier LA ; Newman, Lee S. ; Rose C ; Sawyer RT ; Tinkle SS
• Description:
  Bronchoalveolar lavage (BAL) cells from patients with chronic beryllium disease (CBD) have been used to evaluate the beryllium-specific immune response and potential immunotherapeutics. Beryllium induces interferon-y (IFN-y), interleukin-2 (IL-2), tumour necrosis factor-a (TNF-a), interleukin-6 (IL-6) and interleukin-10 (IL-10) from BAL cells. An antibody to IL-2 and recombinant human (rHu) IL-10 is able to partially suppress the beryllium-stimulated immune response. To obtain BAL cells, bronchoscopy is required, providing risk to the patient and a limited number of cells to study the immune response. As a result, the objectives of the study were to determine 1) whether CBD peripheral blood mononuclear cells (PBMNs) stimulated with beryllium would produce a similar cytokine pattern as BAL cells, and 2) whether this response could be modulated by interleukin-4 (IL-4), an immunomodulatory cytokine. CBD and normal individuals' PBMN and BAL cells were stimulated with and without beryllium sulfate. To modulate this antigen-stimulated response, we added rHu IL-4 to the unstimulated and beryllium-stimulated cells. IFN-y, IL-2, TNF-, IL-6 and IL-10 cytokine concentrations were determined from cell supernatants by enzyme-linked immunosorbent assays (ELISA), while IL-4 messenger ribonucleic acid (mRNA) was assessed using polymerase chain reaction (PCR). Beryllium did not stimulate any of these cytokines from normal PBMNs. Increasing levels of IL-6 and TNF- were produced constituitively by CBD PBMNs over time. Compared to the unstimulated CBD PBMNs, beryllium stimulated significant IFN-y, TNF-a, IL-2, IL-6 and IL-10 production. This response was similar to that stimulated from CBD BAL cells, although of a much lower magnitude. Low levels of IL-4 mRNA were found in CBD and control PBMNs, which were not increased with beryllium stimulation. The beryllium-stimulated cytokine levels were not decreased by the addition of IL-4. IL-4 was unable to downregulate any of these beryllium-stimulated cytokines from CBD BAL cells or increase IL-4 mRNA from either CBD PBMN or BAL cells, and thus is an unlikely immunomodulatory agent in CBD. From the data, it was concluded that chronic beryllium disease peripheral blood mononuclear cells provide a model to study the beryllium-stimulated immune response. Interleukin-4's inability to downregulate any of the beryllium-stimulated cytokines makes it an unlikely therapeutic candidate in chronic beryllium disease. [Description provided by NIOSH]
• Subjects:
  Beryllium Chronic Disease Immune System Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Alveolar-cells Beryllium-compounds Beryllium-disease Chronic-degenerative-diseases Immune-reaction Lung-disease Pulmonary-system-disorders Respiratory-system-disorders
• ISSN:
  0903-1936
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; OSHA Region 3 ; OSHA Region 8 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  403-415
• Volume:
  17
• Issue:
  3
• NIOSHTIC Number:
  nn:20032161
• Citation:
  Eur Respir J 2001 Mar; 17(3):403-415
• Contact Point Address:
  L. Maier, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA
• CAS Registry Number:
  Beryllium (CAS RN 7440-41-7)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  European Respiratory Journal
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9f757cb51764be0c8f1dae01d39efae4ddddd869dc75cd2dacbaad1ee1d51242b0cc8411064f6ce2424ce283a8bb72e0340c18252fd6fc81736ba6ed26ecc1a6
• Download URL:
  https://stacks.cdc.gov/view/cdc/186205/cdc_186205_DS1.pdf
• File Type:
  [PDF - 175.22 KB ]