Production of IL-12, IL-18 and TNF-alpha by alveolar macrophages in hypersensitivity pneumonitis.
OBJECTIVE
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.
Chen
Baomin
B
Department of Pneumology and Allergology, Ruhrlandklinik, Medical Faculty, University of Essen, Germany.
Tong
Zhaohui
Z
Nakamura
Shinobu
S
Costabel
Ulrich
U
Guzman
Josune
J
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000503:physiopathology*; D018929:Cell Culture Techniques; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis*; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12