Proinflammatory cytokines in hypersensitivity pneumonitis

We examined the synthesis and release of the proinflammatory cytokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and interleukin-8 (IL-8) in the context of subjects with hypersensitivity pneumonitis (HP). Subjects with acute HP were found to have alveolar macrophages that released high levels of MIP-1 alpha and IL-8, whereas control subjects had cells that released low levels of these factors. Bronchoalveolar lavage fluid from HP subjects contained low but significant levels of MIP-1 alpha and IL-8. Immunohistochemistry revealed that macrophages from acute HP subjects expressed MIP-1 alpha and IL-8 at high levels. Treatment of acute HP subjects by contact avoidance or by corticosteroids reduced the synthesis of both cytokines. Supernatants of alveolar macrophages from subjects with HP were shown to attract activated CD8+ T lymphocytes, and this activity was significantly inhibited by anti-MIP-1 alpha. MIP-1 alpha and IL-8 may be important inflammatory cytokines in the development of HP via their capacity to attract inflammatory cells (activated CD8+ T lymphocytes and neutrophils, respectively) into the airways of subjects with HP.