{
    "abstract": "Infection-related lipopolysaccharide (LPS) release causes cytokine storm and acute lung injury. Emerging data show that the interleukin 6 (IL-6) inhibitor tocilizumab can improve lung damage in patients with sepsis. This study aimed to investigate the therapeutic effect of tocilizumab on acute lung injury in cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Tocilizumab was administered on post-operative day 21, and LPS was injected intraperitoneally on day 29. Three hours after LPS injection, hemodynamic parameters, biochemistry data, and arterial blood gas analysis were evaluated, along with measurements of IL-6 and tumor necrosis factor-\u03b1 (TNF-\u03b1). Liver and lung histology was examined, and protein levels were analyzed. LPS administration reduced portal pressure, portal venous flow and cardiac index in the BDL rats. In addition, LPS administration induced acute lung injury, hypoxia and elevated TNF-\u03b1 and IL-6 levels. Pre-treatment with tocilizumab did not affect hemodynamic and biochemistry data, but it ameliorated lung injury and decreased TNF-\u03b1, IL-6, and CD68-positive macrophage infiltration. Moreover, tocilizumab administration improved hypoxia and gas exchange in the BDL rats, and downregulated hepatic and pulmonary inflammatory protein expression. In conclusion, LPS administration induced acute lung injury in biliary cirrhotic rats. Pre-treatment with tocilizumab reduces lung damage and hypoxia, possibly by downregulating inflammatory proteins and reducing IL-6, TNF-\u03b1 and CD68-positive macrophage recruitment in the lung.",
    "authors": [
        {
            "affiliation": "Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.",
            "firstname": "Shao-Jung",
            "initials": "SJ",
            "lastname": "Hsu"
        },
        {
            "affiliation": "Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Respiratory Therapy, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.",
            "firstname": "Kuang-Yao",
            "initials": "KY",
            "lastname": "Yang"
        },
        {
            "affiliation": "Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.",
            "firstname": "Hui-Chun",
            "initials": "HC",
            "lastname": "Huang"
        },
        {
            "affiliation": "Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.",
            "firstname": "Chiao-Lin",
            "initials": "CL",
            "lastname": "Chuang"
        },
        {
            "affiliation": "Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: ccchang7@vghtpe.gov.tw.",
            "firstname": "Ching-Chih",
            "initials": "CC",
            "lastname": "Chang"
        },
        {
            "affiliation": "Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.",
            "firstname": "Chon-Kit",
            "initials": "CK",
            "lastname": "Pun"
        },
        {
            "affiliation": "Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.",
            "firstname": "Ming-Chih",
            "initials": "MC",
            "lastname": "Hou"
        },
        {
            "affiliation": "Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.",
            "firstname": "Fa-Yauh",
            "initials": "FY",
            "lastname": "Lee"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2024 Elsevier B.V. All rights reserved.",
    "doi": "10.1016/j.ejphar.2024.176817",
    "journal": "European journal of pharmacology",
    "keywords": [
        "Acute lung injury",
        "Cytokine storm",
        "Lipopolysaccharide",
        "Liver cirrhosis",
        "Tocilizumab"
    ],
    "methods": null,
    "publication_date": "2024-08-02",
    "pubmed_id": "39089462",
    "results": null,
    "title": "Pre-treatment with tocilizumab reduces lipopolysaccharide-induced acute lung injury in biliary cirrhotic rats.",
    "xml": "<Element 'PubmedArticle' at 0x7885041c80e0>"
}