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Biological Monitoring of Low-Dose Interleukin 2 in Humans: Soluble Interleukin 2 Receptors, Cytokines, and Cell Surface Phenotypes

Departments of Hematology and Oncology [E. L. H., A. K., C. S., I. D., T. M., H. K., H. P., J. A.] and Pediatric Surgery [M. H.], Medizinische Hochschule Hanover University Medical Center, D-3000 Hanover 61, Germany

Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, -interferon, tumor necrosis factor-, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2.

In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in -interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor- levels was observed during rIL-2 treatment in vivo.

The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively.

¹ To whom requests for reprints should be addressed, at Abt. Hamatologie u. Onkologie (6860), Medizinische Hochschule Hannover, D-3000 Hannover 61, Germany.

Received 8/22/90. Accepted 9/24/91.