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Interleukin 1 Trials in Cancer Patients: A Review of the Toxicity, Antitumor and Hematopoietic Effects

The University of Michigan Medical Center, Department of Internal Medicine, Division of Hematology/Oncology, Ann Arbor, Michigan, USA

Correspondence: John W. Smith II, M.D., The University of Michigan Medical Center, Department of Internal Medicine, Division of Hematology/Oncology, 3119 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0374, USA. Telephone: 313-936-5281; Fax: 313-936-7376.

Clinical trials of interleukin 1 (IL-1) and IL-1ß have been completed that assess the toxicities of these cytokines as well as their hematopoietic and antitumor effects. Both forms of IL-1 recognize the same cell surface receptors and have similar toxicities and similar biological activities. Toxicities including fever, flu-like symptoms and dose-limiting hypotension can be severe yet manageable, and IL-1 can be given safely to human cancer patients. Most toxicities and biological effects appear to be dose-related. IL-1 alone has little antitumor activity against melanoma, renal cell carcinomas or other malignancies. The hematopoietic effects, including megakaryocytopoietic effects, are modest and are probably not worth the toxicity necessary to achieve them. However, IL-1 seems to endow certain progenitor cells with responsiveness to other hematopoietic cytokines including colony-stimulating factors and IL-3. One potential application of IL-1 is to help expand bone marrow ex vivo following stem cell harvest, which could allow further chemotherapy dose escalations in chemotherapy-sensitive tumors.

Key Words. Interleukin 1 • Neoplasms • Review • Clinical trials • Toxicity • Antitumor effects • Hematopoietic effects