Tumor necrosis factor alpha mediates the antitumor effect of combined interleukin-2 and whole body hyperthermia

The Journal of Surgical Research
K L FritzA T Lefor

Abstract

Combined whole body hyperthermia (WBHT) and interleukin-2 (IL-2) significantly reduces the growth rate of subcutaneous 10 day MCA-105 tumors in C57BL/6 mice, but not in 3-day tumors. Others have shown that macroscopic tumors show reduced growth with tumor necrosis factor alpha (TNF alpha) therapy compared with microscopic tumors. We sought to determine if the antitumor effect of combined WBHT+IL-2 is mediated by TNF alpha. After inducing MCA-105 sarcoma in the right hind limb on Day 0, C57BL/6 mice were randomized to treatment groups (six each) on Day 10: control, WBHT alone, IL-2 alone, and WBHT+IL-2. Pooled serum was assessed by ELISA for TNF alpha level: control (350 pg/ml), WBHT (250 pg/ml), IL-2 alone (>2450 pg/ml), and WBHT+IL-2 (>2450 pg/ml). Using the same tumor model, animals were treated in the following groups: control, WBHT+IL-2, anti-TNF alpha Ab alone, and WBHT+IL-2+Ab. Mice in the control, Ab alone, and WBHT+IL-2+Ab groups had similar tumor growth rates (P > 0.05). However, the growth rate for WBHT+IL-2 was significantly lower (P < 0.05) compared to the other three groups. These data demonstrate significantly increased TNF alpha levels in mice treated with combined therapy and abrogation of the antitumor effect o...Continue Reading

Citations

May 16, 2000·Tropical Medicine & International Health : TM & IH·G BiembaG Weiss
Sep 21, 2001·British Journal of Haematology·A Luther-WyrschA Wodnar-Filipowicz
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·I M ConboyP P Jones

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