Mediators of hypersensitivity pneumonitis

J Lab Clin Med. 2000 Jul;136(1):29-38. doi: 10.1067/mlc.2000.107694.


Inhalation of Saccharopolyspora rectivirgula (S. rectivirgula) causes farmer's lung disease, a classic example of hypersensitivity pneumonitis (HP). HP is characterized by bronchoalveolar lavage fluid (BALF) neutrophilia (within the first 48 hours after inhalation), followed by BALF lymphocytosis. We utilized a well-described murine model of HP to determine the timing of the appearance of the C-C chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha); the inflammatory cytokines tumor necrosis factor (TNF), interleukin-1alpha (IL-1alpha), and interleukin-6 (IL-6); and the Th1 -differentiating cytokine interleukin-12 (IL-12) in BALF. After a single intratracheal administration of S. rectivirgula, there was remarkable BALF neutrophilia (peak 24 to 48 hours), followed by a BALF lymphocytosis (peak 48 to 72 hours) in both C57Bl/6 and BALB/c mice that was preceded by the appearance of MIP-1alpha in BALF (peak 4 to 6 hours) and MCP-1 (peak at 48 hours). In both strains of mice there was a striking increase of BALF IL-12 (peak 48 to 72 hours). There was also an increase in BALF IL-6, IL-1alpha, and TNF that was greater in the BALB/c mice than in the C57Bl/6 mice. S. rectivirgula induced the secretion of MIP-1alpha, MCP-1, IL-6, IL-1alpha, and IL-12 from the murine macrophage cell line J774A.1; MIP-1alpha, IL-6, IL-1alpha, IL-12, and TNF from C57Bl/6 alveolar macrophages; and IL-1alpha, IL-6, and TNF-but not IL-12-from BALB/c alveolar macrophages. We conclude that chemokines and cytokines induced by intratracheal administration of S. rectivirgula precede BALF neutrophilia and lymphocytosis and may cause differentiation of Th1 cells; we also conclude that pulmonary macrophages represent a potential source of these substances.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alveolitis, Extrinsic Allergic / immunology*
  • Alveolitis, Extrinsic Allergic / pathology*
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokine CCL2 / metabolism
  • Chemokine CCL3
  • Chemokine CCL4
  • Interleukin-12 / metabolism
  • Interleukin-6 / metabolism
  • Leukocyte Count
  • Lymphocytes
  • Macrophage Inflammatory Proteins / metabolism
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neutrophils
  • Tumor Necrosis Factor-alpha / metabolism


  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Interleukin-6
  • Macrophage Inflammatory Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-12