Background and aim of the work: Hypersensitivity pneumonitis (HP) is characterized by a macrophage-lymphocyte alveolitis and granuloma formation. A wide range of cytokines have been implicated in the pathophysiology and development of granulomas in HP, but there is no information about the production of interleukin-12 (IL-12) and IL-18 by alveolar macrophages (AM) in human HP. We evaluated whether the production of IL-12, IL-18 and tumor necrosis factor-alpha (TNF-alpha) is locally increased in HP, and whether there is a correlation between these cytokines, as well as with the cellular profile of bronchoalveolar lavage (BAL) fluid in HP.
Methods: AM from 11 patients with HP and 10 control subjects were cultured for 24h in 10% RPMI medium alone, or with RPMI medium and lipopolysaccharide (LPS) (100 ng/ml). Cytokines in the culture supernatants were assayed by ELISA.
Results: The production of IL-18 and TNFalpha was increased in patients with HP in either absence or presence of LPS compared with controls. Although the spontaneous production of IL-12 was low, with LPS stimulation it was significantly elevated in HP. The concentration of the LPS-stimulated IL-12 production positively correlated with the percentage of lymphocytes (r = 0.72, p = 0.011), and negatively correlated with the percentage of macrophages (r = -0.88, p < 0.001).
Conclusions: These observations suggest that IL-12, IL-18 and TNFalpha may be involved in the pathogenesis of HP.