Published on:
    Journal of Cardiovascular Disease Research, 2010; 1(1):29-36
    Invented Review | doi:10.4103/0975-3583.59983

    The Dual Role of TNF in Pulmonary Edema


    Guang Yang, M.D. & Ph.D.,*, Jürg Hamacher, M.D.†, Groshkov Boris, Ph.D.*, Richard White, Ph.D.‡, Supriya Sridhar, Ph.D.*, Alexander Verin, Ph.D.*, Trinad Chakraborty, Ph.D.§, Rudolf Lucas, Ph.D*

    Pulmonary Division, University Hospital, University of Bern, Bern, Switzerland;

    Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA, USA;

    §Institute of Medical Microbiology, Justus-Liebig University of Giessen, Giessen, Germany;

    *Correspondence to: Dr. Guang Yang, Vascular Biology Center, Medical College of Georgia, Augusta, GA,30912,USA. E-mail:;

    *Dr. Rudolf Lucas, Vascular Biology Center & Dept. of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA, 30912, USA. E-mail:


    ABSTRACT—Pulmonary edema, a major manifestation of left ventricular heart failure, renal insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states, is a significant medical problem worldwide and can be life-threatening. The proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute to the pathogenesis and development of pulmonary edema. However, some recent studies have demonstrated surprisingly that TNF can also promote alveolar fluid reabsorption in vivo and in vitro. This protective effect of the cytokine is mediated by the lectin-like domain of the cytokine, which is spatially distinct from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the lectinlike domain of TNF, can significantly increase alveolar fluid clearance and improve lung compliance in pulmonary edema models. In this review, we will discuss the dual role of TNF in pulmonary edema. Abbreviations:—tumor necrosis factor (TNF); acute lung injury (ALI); acute respiratory distress syndrome (ARDS); positive end-expiratory pressure (PEEP);epithelial sodium channel (ENaC);neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2);serum and glucocorticoid dependent kinase (Sgk-1);insulin-like growth factor 1 (IGF-1);Protein Kinase C (PKC);reactive oxygen species (ROS);myosin light chain (MLC);pneumolysin (PLY);listeriolysin (LLO);interleukin (IL);bronchoalveolar lavage fluids (BALF);Bacillus Calmette-Guerin (BCG);TNF receptor type 1 (TNFR1); TNF receptor type 2 (TNF-R2).

    Keywords: TNF; pulmonary edema; cytokine; sodium transport; hyperpermeability; reactive oxygen species