Barna Barbara P, Dweik Raed A, Farver Carol F, Culver Daniel, Yen-Lieberman Belinda, Thomassen Mary Jane
Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA.
Clin Immunol. 2002 May;103(2):169-75. doi: 10.1006/clim.2002.5211.
In chronic beryllium disease (CBD), a granulomatous lung disease characterized by hypersensitivity to beryllium salts (BE), BE challenge of bronchoalveolar lavage cells induces IFNgamma. Although nitric oxide (NO) is elevated in CBD airways, the effects of NO on CBD IFNgamma responses are unknown. Here we report that BE-stimulated IFNgamma production in CBD lavage cells was markedly reduced (74%) by the NO generator DETA NONOate. Investigation of IFNgamma-stimulatory cytokine involvement indicated that lavage cell IL-18 was significantly increased (fourfold) by BE and reduced (64%) by DETA NONOate but IL-12 was undetectable. IL-18 production was caspase-1-dependent but caspase 1 inhibition reduced IFNgamma only partially (43%). Specific antibody depletion of lavage cell IL-18 yielded marginal reduction (19%) of IFNgamma. Data are the first to show that: (1) BE stimulates IL-18 as well as IFNgamma in CBD; (2) BE cytokine responses are NO-sensitive; and (3) NO down-regulation of IFNgamma involves other sites in addition to IL-18.
在慢性铍病（CBD）中，这是一种以对铍盐（BE）过敏为特征的肉芽肿性肺病，支气管肺泡灌洗细胞的BE激发可诱导γ干扰素。尽管CBD气道中的一氧化氮（NO）水平升高，但NO对CBD中γ干扰素反应的影响尚不清楚。在此我们报告，NO供体DETA NONOate可使CBD灌洗细胞中BE刺激的γ干扰素产生显著减少（74%）。对γ干扰素刺激细胞因子参与情况的研究表明，BE可使灌洗细胞白细胞介素-18显著增加（四倍），而DETA NONOate可使其减少（64%），但未检测到白细胞介素-12。白细胞介素-18的产生依赖于半胱天冬酶-1，但半胱天冬酶-1抑制仅使γ干扰素部分减少（43%）。灌洗细胞白细胞介素-18的特异性抗体清除使γ干扰素产生仅略有减少（19%）。这些数据首次表明：（1）BE在CBD中可刺激白细胞介素-18以及γ干扰素；（2）BE细胞因子反应对NO敏感；（3）NO对γ干扰素的下调除白细胞介素-18外还涉及其他位点。
