• The Dual Role of TNF in Pulmonary Edema

      Yang, Guang; Hamacher, Jürg; Gorshkov, Boris A; White, Richard E.; Sridhar, Supriya; Verin, Alexander D.; Chakraborty, Trinad; Lucas, Rudolf; Department of Pharmacology and Toxicology; Vascular Biology Center (2010)
      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 lectin-like 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.