Interleukin 12, interleukin 18, and tumor necrosis factor α release by alveolar macrophages: acute and chronic hypersensitivity pneumonitis

Abstract

Hypersensitivity pneumonitis (HP) is characterized by a granulomatous inflammation and may show various forms of clinical presentation, such as the acute, subacute, and chronic forms. The TH1-associated cytokines interleukin (IL) 12 and IL-18 and tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of both the acute and chronic forms of HP. To compare the release of IL-12, IL-18, and TNF-alpha from bronchoalveolar lavage (BAL) macrophages in these 2 forms of HP. Patients underwent BAL 0 to 6 days after the last antigen exposure. Alveolar macrophages (AMs) from BAL in 6 patients with acute HP, 16 with chronic HP, and 11 controls were cultured for 24 hours. Cytokines in the culture supernatants were measured by enzyme-linked immunosorbent assay. The production of IL-12, IL-18, and TNF-alpha by AMs was increased in patients with both acute and chronic forms in either the absence or presence of lipopolysaccharide compared with controls. The levels of IL-12, IL-18, and TNF-alpha showed no difference between patients with acute and chronic HP. The spontaneous production of IL-12, IL-18, and TNF-alpha did not correlate with the CD4/CD8 ratio in BAL. The spontaneous and lipopolysaccharide-stimulated release of IL-12 showed a positive correlation with the percentage of lymphocytes (r = .470, P = .03; r = .496, P = .02; respectively) in BAL. This study demonstrates that an increased release of IL-12, IL-18, and TNF-alpha by AMs is associated with both the acute and chronic forms of HP.