Patterns of cytokines released by peripheral blood leukocytes of normal donors and cancer patients during interleukin-2 activation in vitro

Sherry Dupere, Nicholas Obiri, Alan Lackey, Dennis Emma, John Yannelli, Douglas Orr, Robert Birch, Timothy E. O'Connor

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-γ (IFN-γ), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-γ, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (<300 pg/ml) and minimal levels of IFN-γ, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients. The production of cytokines may have therapeutic relevance since the level of leukocytosis induced by the IL-2 priming of the patients in vivo paralleled the level of subsequent TNF production upon IL-2 stimulation in vitro. In contrast to these findings on cytokine induction, all patient PBLs after stimulation with IL-2 in vitro showed the capacity to kill NK-sensitive K562 and LAK-sensitive Daudi target cells but at levels that showed no obvious relationship to either patient leukocytosis or levels of cytokine production.

Original languageEnglish
Pages (from-to)140-148
Number of pages9
JournalJournal of Biological Response Modifiers
Issue number2
StatePublished - Apr 1990


  • Adoptive cell therapy
  • Cytokines
  • Interferon
  • Interleukin-2
  • Lymphokine-activated killer cells
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research


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