Local hyperthermia abrogates the anti-immunotherapeutic effect of interleukin-8

The therapeutic efficacy of cellular immunotherapy depends not only on the anti‐tumor activity of the administered effector cells but also on their ability to gain access to the tumor by extravasation. Although interleukin‐8 (IL‐8) has been shown to prevent the vascular leak associated with IL‐2, it also abrogates the anti‐tumor effect of IL‐2. We undertook these studies to determine if LHT could abrogate the anti‐immunotherapeutic effect of IL‐8, since IL‐8 inhibits leukocyte adhesion. C57BL/6 mice were divided into four groups of six animals each after induction of MCA‐105 fibrosarcoma inoculated into the right bindlimb on day 0 and were treated begining on day 3 as follows: no therapy, IL‐2 alone (1.02 × 106 IU ip tid on days 3‐7), IL‐2 + IL‐8 (9.6 ng ip tid on days 3–7), and IL‐2 + IL‐8 + LHT (45C × 15 min on days 3, 5, and 7). Tumor growth was measured on days 10–21 and analyzed by Wilcoxon rank‐sum analysis. IL‐2 reduced tumor growth significantly (P < 0.05) compared to no therapy, and IL‐8 abrogated the anti‐tumor effect of IL‐2, resulting in tumor growth in animals receiving IL‐2 + IL‐8, similar to the no therapy group (P > 0.05). However, addition of LHT to IL‐2 + IL‐8 resulted in significantly (P < 0.05) less tumor growth than no therapy or IL‐2 + IL‐8. Activity of the mice was scored as an indicator of systemic toxicity. We found that IL‐8 was able to increase the activity (P = 0.07) of the mice when administered with IL‐2. These results suggest that IL‐8 may protect the tumorbearing animal from the systemic toxicity of IL‐2, while LHT abrogates the anti‐immunotherapeutic effect of IL‐8. © 1994 Wiley‐Liss, Inc.