Journal of Clinical Oncology, Vol 9, 694-704, Copyright © 1991 by American Society of Clinical Oncology
Interleukin-2 toxicity
JP Siegel and RK Puri
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD.
Because of the ability of interleukin-2 (IL-2) to support the proliferation
and activation of numerous types of immunocompetent cells and to support
the survival of adoptively transferred lymphocytes, there has been
considerable interest in its use in the immunotherapy of malignancies.
While studies to date have indicated that IL-2 has activity against some
malignancies, considerable toxicity has also been observed. Careful
prescreening and selection of patients and appropriate management of
toxicity can minimize adverse outcomes. Studies of IL-2 effects have
provided intriguing evidence of interactions of the immune/cytokine system
with the neuroendocrine, cardiovascular, and other systems. Studies in
animal models have demonstrated the central role of an intact immune system
in mediating many toxicities of IL-2. Several adverse effects of IL-2
appear to be mediated by other cytokines whose production is induced by
IL-2. Studies into the pathogenesis and manifestations of IL-2 toxicity
have offered the hope of developing less toxic approaches to IL-2 therapy.
Several lessons from the IL-2 experience are likely to be applicable in the
clinical development of other cytokines.
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