Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, 94305, USA.
Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA; Department of Medicine, Division of Infectious Disease, Stanford University, Stanford, CA, 94305, USA.
Biomaterials. 2019 May;203:52-62. doi: 10.1016/j.biomaterials.2019.02.017. Epub 2019 Feb 22.
Idiopathic pulmonary fibrosis (IPF) is a life-threatening progressive lung disorder with limited therapeutic options. While interleukin-10 (IL-10) is a potent anti-inflammatory and anti-fibrotic cytokine, its utility in treating lung fibrosis has been limited by its short half-life. We describe an innovative hydrogel-based approach to deliver recombinant IL-10 to the lung for the prevention and reversal of pulmonary fibrosis in a mouse model of bleomycin-induced lung injury. Our studies show that a hyaluronan and heparin-based hydrogel system locally delivers IL-10 by capitalizing on the ability of heparin to reversibly bind IL-10 without bleeding or other complications. This formulation is significantly more effective than soluble IL-10 for both preventing and reducing collagen deposition in the lung parenchyma after 7 days of intratracheal administration. The anti-fibrotic effect of IL-10 in this system is dependent on suppression of TGF-β driven collagen production by lung fibroblasts and myofibroblasts. We conclude that hydrogel-based delivery of IL-10 to the lung is a promising therapy for fibrotic lung disorders.
特发性肺纤维化（IPF）是一种危及生命的进行性肺部疾病，治疗选择有限。虽然白细胞介素 10（IL-10）是一种有效的抗炎和抗纤维化细胞因子，但由于其半衰期短，其在治疗肺纤维化方面的应用受到限制。我们描述了一种基于水凝胶的创新方法，将重组 IL-10 递送到肺部，以预防和逆转博莱霉素诱导的肺损伤小鼠模型中的肺纤维化。我们的研究表明，透明质酸和肝素基水凝胶系统通过利用肝素可逆结合 IL-10 而不引起出血或其他并发症的能力，局部递送电 IL-10。与可溶性 IL-10 相比，这种制剂在气管内给药 7 天后对预防和减少肺实质中的胶原沉积更有效。该系统中 IL-10 的抗纤维化作用依赖于抑制 TGF-β 驱动的肺成纤维细胞和肌成纤维细胞产生胶原。我们得出结论，将 IL-10 递送到肺部的水凝胶基疗法是治疗纤维化肺部疾病的一种有前途的疗法。
