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Transient decrease in IL-2-responsive lymphocytes 24 hours after initiation of continuous IL-2 infusion in cancer

G Weil-Hillman1, J A Hank, N S Rosenthal

  • 1Department of Human Oncology, University of Wisconsin, Madison.

Journal of Biological Response Modifiers
|October 1, 1988
PubMed
Summary
This summary is machine-generated.

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Recombinant interleukin-2 (IL-2) therapy caused a temporary drop in cancer patients' circulating lymphocytes. However, these lymphocytes recovered and showed enhanced natural killer (NK) and proliferative functions with subsequent IL-2 cycles.

Area of Science:

  • Immunology
  • Cancer Therapy
  • Clinical Research

Background:

  • Recombinant interleukin-2 (IL-2) is used in cancer treatment.
  • The effects of IL-2 on circulating lymphocytes during therapy are not fully understood.

Purpose of the Study:

  • To investigate the transient decrease in peripheral blood lymphocytes (PBLs) during IL-2 therapy.
  • To assess the functional recovery and activation of lymphocytes during IL-2 treatment cycles.

Main Methods:

  • Phase I clinical trial involving cancer patients receiving continuous intravenous IL-2 infusions.
  • Monitoring of circulating PBL counts and their in vitro natural killer (NK) and IL-2 induced proliferative responses.
  • Lymphocyte mixing experiments to evaluate potential suppressor cell activity.

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Main Results:

  • A transient 80% decrease in circulating PBLs was observed 24 hours into each IL-2 cycle.
  • Lymphocyte NK and proliferative activity was reduced early in therapy but recovered by the end of infusions.
  • Subsequent IL-2 cycles showed PBLs with progressively increasing in vitro NK and proliferative activity, exceeding pre-therapy levels by the fourth cycle.
  • Mixing experiments did not support a suppressor cell mechanism for the initial drop in lymphocyte activity.

Conclusions:

  • IL-2 causes a transient depletion of circulating lymphocytes at the start of each treatment cycle.
  • Lymphocyte function is impaired only during the initial IL-2 cycle.
  • Resting IL-2 responsive cells initially leave circulation but become activated and detectable with repeated IL-2 exposure.