Diabetes mellitus induced by low-dose interleukin-2.
Interleukin-2 (IL-2) is a potent immunomodulator that has been associated with the clinical development of autoimmune disorders. However, diabetes mellitus has not been reported in patients treated with single-agent IL-2. We conducted a clinical trial of a protracted daily schedule of subcutaneously administered low-dose IL-2. A patient with advanced colorectal cancer, treated with 1.5 x 10(6) international units of IL-2 daily, developed insulin-requiring diabetes during therapy. Hyperglycemia improved during treatment interruption and recurred with reinstitution of IL-2. The diabetes in this patient developed in the context of T cell and natural killer cell expansion, and the presence of islet cell autoantibodies was documented. We postulate that, in this patient, IL-2 reversed the anergy of autoreactive T cells that had escaped clonal deletion. It is possible that prolonged daily exposure to immunomodulatory doses of IL-2 will result in the development of autoimmune phenomena not observed with other schedules of administration.
Soni
N
N
Division of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Meropol
N J
NJ
Porter
M
M
Caligiuri
M A
MA
D000276:Adjuvants, Immunologic / Q000009:adverse effects; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects*; D018655:Lymphocyte Count / Q000187:drug effects; D008875:Middle Aged; D013997:Time Factors
D000276:Adjuvants, Immunologic; D007376:Interleukin-2