Cardiopulmonary toxicity of adoptive immunotherapy

Am J Med Sci. 1988 Dec;296(6):406-12. doi: 10.1097/00000441-198812000-00007.


Adoptive immunotherapy, the administration of interleukin-2 (IL-2) and interleukin-2 activated cells, leads to tumor regression in some patients with advanced cancer. Although this new therapeutic modality offers hope for the future, at present, a multitude of toxicities limit the total dose and duration of therapy. Among the toxic side effects a purported third space or vascular leak syndrome is the most serious. In this review, we detail the evidence for a third space syndrome (peripheral edema, ascites, oliguria, elevated serum creatinine levels) and cardiopulmonary dysfunction (hypotension, respiratory distress, pulmonary edema, hypoxemia) with adoptive immunotherapy in human and animal studies. We conclude that IL-2 administration is associated with increased pulmonary microvascular permeability, infiltration of the lung parenchyma with large esterase negative lymphoid cells, hypoxemia, systemic hypotension, positive fluid balance and, in animals, transient pulmonary hypertension. These abnormalities do not seem to be caused by IL-2 directly; the causes may be mediated by IL-2 activated lymphocytes or other IL-2 activated cellular mediators.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Gas Analysis
  • Capillary Permeability
  • Heart Diseases / etiology*
  • Hemodynamics
  • Humans
  • Immunization, Passive / adverse effects*
  • Interleukin-2 / adverse effects
  • Killer Cells, Natural / immunology
  • Lung Diseases / etiology*
  • Lymphocyte Activation
  • Neoplasms / therapy*
  • Pulmonary Alveoli / blood supply


  • Interleukin-2