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Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural delivery in pleural infection patients
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  • Published on:
    RE: Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural delivery in pleural infection patients
    • Nikolaos I. Kanellakis, Postdoctoral Researcher Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
    • Other Contributors:
      • John M. Wrightson, Consultant
      • Ioannis Psallidas, Associate Professor
      • Najib M. Rahman, Clinical Lecturer

    We are grateful that scientists around the world are showing interest in our research, and delighted to reply to comments from Creaney et al. with regards to our paper the “Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural delivery in pleural infection patients”.[1]
    Pleural infection is a significant clinical entity, has increasing incidence worldwide and is associated with high morbidity, mortality and burden to healthcare services. Effective treatment still relies upon effective pleural fluid drainage, and thus investigation of the pathological mechanisms behind fluid formation and treatment response is key to improving care.
    The MIST2 study demonstrated that intrapleural delivery of tissue plasminogen activator (t-PA) alone or t-PA plus DNase increased volume of pleural fluid drained in humans with pleural infection, in a placebo controlled double blind randomised study.[2 ] Although the exact biological mechanisms via which t-PA induces the volume increment of drained pleural fluid are unknown, the design of the MIST2 study means that we are confident in the biological observation of increased fluid production in response to t-PA administration. Lansley et al. have demonstrated that the chemokine MCP-1 (also known as CCL-2) is the key protein that upon intrapleural t-PA administration induces fluid formation in healthy mice.[3]
    We designed a study to directly assess their hypothesis in human pleural infection patients fo...

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    Conflict of Interest:
    None declared.
  • Published on:
    Induction of monocyte chemotactic protein-1 by intrapleural instillation of tissue plasminogen activator
    • Jenette CREANEY, Professor University of Western Australia, Perth, Australia
    • Other Contributors:
      • Hui Min CHEAH, Research Assistant
      • Georgious T. STATHPOULOS, Professor
      • Ioannis KALOMENIDIS, Assistant Professor and Consultant
      • Y. C. Gary Lee, Professor

    Monocyte chemotactic protein (MCP)-1 has raised interests concerning its role in pleural
    fluid formation. Recent preclinical studies have found that antagonists against MCP-1
    reduces formation of malignant pleural effusions from lung cancer1 and mesothelioma as
    well as from benign (carrageenan-induced) pleuritis2 in murine models. In humans,
    longitudinal collection of malignant effusions via indwelling pleural catheters also showed a
    rise in MCP-1 level over time.3

    In humans and animals, pleural instillation of fibrinolytics such as tissue plasminogen
    activator (tPA) consistently generates large volume of pleural fluid formation in healthy as
    well as in various pleural disease states4, 5. In mice, MCP-1 antagonists also decrease tPA-induced
    fluid formation.6

    We therefore read with interest the work by Kanellakis et al7 on measuring MCP-1
    concentration in pleural fluid samples collected from patients in the MIST (Multicentre
    Intrapleural Sepsis Trial)-24 who were given tPA or placebo.

    The study by Kanellakis et al7 highlights the challenges and limitations of using clinical
    samples/data to decipher biological signals. They reported that following tPA installation,
    MCP-1 level in pleural fluid increased. However, the pleural fluid MCP-1 levels were similar,
    and not significantly higher, in the tPA-treated patients compared with those who did not
    receive tPA.

    We sug...

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    Conflict of Interest:
    None declared.