Rolfe M W, Standiford T J, Kunkel S L, Burdick M D, Gilbert A R, Lynch J P, Strieter R M
University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor 48109-0360.
Am Rev Respir Dis. 1993 Nov;148(5):1378-84. doi: 10.1164/ajrccm/148.5.1378.
Sarcoidosis is a systemic granulomatous disease with a marked propensity for involvement of the pulmonary parenchyma and thoracic lymphatic system. This granulomatous process is characterized by aggregations of mononuclear cells, multinucleated giant cells, and variable degrees of fibrosis. The agent(s) responsible for the initiation of the inflammatory granulomatous process remain unknown. Interleukin-1 beta (IL-1) is a cytokine that has been shown to possess potent proinflammatory properties and is likely to play a role in mediating many of the immunopathologic events observed in sarcoidosis. Despite the degree of granulomatous inflammation, both the pulmonary and systemic pathogenic changes associated with sarcoidosis have a remarkable propensity for spontaneous resolution. The interleukin-1 receptor antagonist (IRAP), an endogenous inhibitor of IL-1 bioactivity, may have a critical role as an in vivo immunomodulator of IL-1-dependent granulomatous inflammation of sarcoidosis. In this study we demonstrate constitutive expression of IRAP mRNA and antigen from bronchoalveolar lavage fluid cells and cell-free fluid, respectively, obtained from both normal subjects and patients with sarcoidosis. However, immunolocalization of IRAP was found to be significantly localized to the sarcoid granuloma as compared with the uninvolved lung interstitium. Our findings indicate that IRAP expression is compartmentalized (granuloma) within the interstitium of patients with sarcoidosis. Thus, IRAP may function as an important in vivo immunomodulator of granulomatous inflammation.
结节病是一种全身性肉芽肿性疾病，显著倾向于累及肺实质和胸内淋巴系统。这种肉芽肿性病变的特征是单核细胞、多核巨细胞聚集以及不同程度的纤维化。引发炎症性肉芽肿病变的病原体尚不清楚。白细胞介素-1β（IL-1）是一种细胞因子，已被证明具有强大的促炎特性，可能在介导结节病中观察到的许多免疫病理事件中发挥作用。尽管存在肉芽肿性炎症程度，但与结节病相关的肺部和全身性致病变化都有显著的自发缓解倾向。白细胞介素-1受体拮抗剂（IRAP）是IL-1生物活性的内源性抑制剂，可能作为结节病IL-1依赖性肉芽肿性炎症的体内免疫调节剂发挥关键作用。在本研究中，我们分别从正常受试者和结节病患者获取的支气管肺泡灌洗细胞和无细胞液中，证实了IRAP mRNA和抗原的组成性表达。然而，与未受累的肺间质相比，发现IRAP的免疫定位显著定位于结节病肉芽肿。我们的研究结果表明，IRAP表达在结节病患者的间质内（肉芽肿）是分隔的。因此，IRAP可能作为肉芽肿性炎症的重要体内免疫调节剂发挥作用。
