Cytokine-Induced Vascular Leak Syndrome

The vascular leak syndrome (VLS) is a major dose-limiting toxicity of cytokine therapy. VLS is characterized by an increase in vascular permeability resulting in tissue edema and, ultimately, multiple organ failure. The most frequent clinical manifestations of cytokine-induced VLS include weight gain, edema, oliguria, hypotension, and dyspnea. Respiratory insufficiency requiring mechanical ventilation and hypotension requiring pressor support have been described as the most severe manifestations of VLS. The pathogenesis of vascular damage is complex and can involve activation of endothelial cells and leukocytes, release of cytokine and inflammatory mediators, and alterations in cell-cell and cell-matrix adhesion with disturbance of vascular integrity. A better understanding of these mechanisms may lead to the development of interventions that will improve the therapeutic efficacy of cytokines. This chapter discusses the clinical manifestation, possible mechanisms, and therapeutic modalities for VLS induced by cytokine therapy.