Mediators of hypersensitivity pneumonitis

Abstract

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-1α (MIP-1α); the inflammatory cytokines tumor necrosis factor (TNF), interleukin-1α (IL-1α), 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-1α 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-1α, and TNF that was greater in the BALB/c mice than in the C57Bl/6 mice. S. rectivirgula induced the secretion of MIP-1α, MCP-1, IL-6, IL-1α, and IL-12 from the murine macrophage cell line J774A.1; MIP-1α, IL-6, IL-1α, IL-12, and TNF from C57Bl/6 alveolar macrophages; and IL-1α, 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. (J Lab Clin Med 2000;136:29-38)