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Abstract：
Interstitial lung diseases (ILDs) are characterized by inflammation or fibrosis of the pulmonary parenchyma. Despite the involvement of immune cells and soluble mediators in pulmonary fibrosis, the influence of antimicrobial peptides (AMPs) remains underexplored. These effector molecules display a range of activities, which include immunomodulation and wound repair. Here, we investigate the role of AMPs in the development of fibrosis in ILD. We compare the concentration of different AMPs and different cytokines in 46 fibrotic (F-ILD) and 17 non-fibrotic (NF-ILD) patients by ELISA and using peripheral blood mononuclear cells from in vitro stimulation in the presence of lysozyme or secretory leukocyte protease inhibitor (SLPI) from 10 healthy donors. We observed that bronchoalveolar lavage (BAL) levels of AMPs were decreased in F-ILD patients (lysozyme: p < 0.001; SLPI: p < 0.001; LL-37: p < 0.001; lactoferrin: p = 0.47) and were negatively correlated with levels of TGF-β (lysozyme: p = 0.02; SLPI: p < 0.001) and IL-17 (lysozyme: p < 0.001; SLPI: p < 0.001). We observed that lysozyme increased the percentage of CD86+ macrophages (p < 0.001) and the production of TNF-α (p < 0.001). We showed that lysozyme and SLPI were associated with clinical parameters (lysozyme: p < 0.001; SLPI: p < 0.001) and disease progression (lysozyme: p < 0.001; SLPI: p = 0.01). These results suggest that AMPs may play an important role in the anti-fibrotic response, regulating the effect of pro-fibrotic cytokines. In addition, levels of lysozyme in BAL may be a potential biomarker to predict the progression in F-ILD patients.
摘要：
间质性肺病(ILD)的特征在于肺实质的炎症或纤维化。尽管免疫细胞和可溶性介质参与肺纤维化,抗菌肽（AMP）的影响仍未充分开发。这些效应分子表现出一系列的活性，其中包括免疫调节和伤口修复。这里,我们研究了AMPs在ILD纤维化发展中的作用。我们通过ELISA比较了46例纤维化（F-ILD）和17例非纤维化（NF-ILD）患者中不同AMP和不同细胞因子的浓度，并使用来自10例健康供体的溶菌酶或分泌性白细胞蛋白酶抑制剂（SLPI）存在下的体外刺激的外周血单核细胞。我们观察到F-ILD患者的支气管肺泡灌洗（BAL）AMPs水平降低（溶菌酶：p<0.001；SLPI：p<0.001；LL-37：p<0.001；乳铁蛋白：p=0.47），并且与TGF-β（溶菌酶：p=0.02；SLPI：p<0.001）和IL-17（溶菌酶：p<0.001；SLp：p）水平呈负相关。我们观察到溶菌酶增加了CD86+巨噬细胞的百分比(p<0.001)和TNF-α的产生(p<0.001)。我们发现溶菌酶和SLPI与临床参数（溶菌酶：p<0.001；SLPI：p<0.001）和疾病进展（溶菌酶：p<0.001；SLPI：p=0.01）相关。这些结果表明，AMPs可能在抗纤维化反应中起重要作用。调节促纤维化细胞因子的作用。此外,BAL中溶菌酶水平可能是预测F-ILD患者病情进展的潜在生物标志物.
