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Synergy of Human Recombinant Interleukin 1 with Interleukin 2 in the Generation of Lymphokine-activated Killer Cells¹

Department of Tumor Biology [W. L. C., L. B. O-S., E. A. G.] and General Surgery [E. A. G.], University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030

Peripheral blood mononuclear cells cultured in vitro with interleukin 2 (IL-2) become cytolytic towards both autologous and allogeneic tumor cells. We report here that IL-1 synergizes with IL-2 in serum-free conditions to produce increased (1.3-286-fold) lymphokine-activated killer (LAK) activity. The most dramatic synergy is seen with low IL-2 concentrations (10 U/ml, 222 pM) and 50–250 U/ml IL-1 or ß. Kinetics of addition experiments demonstrate a specific requirement for IL-1 at or before addition of IL-2 to the culture. We postulate that one of the mechanisms whereby IL-1 augments LAK activity is by rendering LAK-precursors more responsive to IL-2. Up-regulation of the IL-2 receptor ß chain (Tac) and increased [³H]thymidine incorporation in cultures containing IL-1 and IL-2 support this view. In some instances, IL-1 alone is capable of maintaining/generating a small degree of cytolytic activity. Collectively, our data demonstrate that IL-1 is capable of interacting with low dose IL-2 to significantly augment LAK activity, potentially playing an important role in the early stages of LAK activation and differentiation. Because synergy is observed with dramatically reduced IL-2 concentrations, this system may offer an alternative approach to high dose IL-2 therapy for the treatment of neoplastic disease.

¹ This investigation was supported in part by PHS Grant CA47806 awarded by the National Cancer Institute, DHHS, and in part by an award from the Preuss Foundation.

² To whom requests for reprints should be addressed, at Department of Tumor Biology, P. O. Box 79, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.

Received 3/ 9/88. Revised 6/15/88. Revised 9/30/88. Accepted 10/ 5/88.

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