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Physiology and Pharmacology of Temperature Regulation

Patients with solid tumors treated with high-temperature whole body hyperthermia show a redistribution of naive/memory T-cell subtypes

Departments of ¹Oncology/Hematology, ²Clinical Chemistry, ³Anaesthesiology, and ⁴Sports Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Submitted 10 January 2005 ; accepted in final form 24 October 2005

An activation of the immune system might contribute to the therapeutic effect of whole body hyperthermia (WBH) in cancer patients. We explored immune and endocrine responses in patients undergoing high-temperature WBH. Identical parameters were investigated in a separate group of healthy volunteers undergoing physical exercise to rule out effects of sympathetic activation. Lymphocyte subpopulations, lymphocytic expression of a range of adhesion molecules, and serum concentrations of a variety of hormones and cytokines were assessed in cancer patients undergoing high-temperature (60 min at 41.0–41.8°C) WBH (n = 25) and in a separate group of healthy volunteers (n = 10) performing strenuous physical exercise. WBH induced an increase in human growth hormone (hGH), ACTH, and cortisol as well as in TNF-, IL-6, IL-8, and IL-12R. We observed an increase in natural killer (NK) cells and CD56⁺ NK T cells shortly after initiation of WBH. In contrast, we found a decrease in T cells expressing L-selectin (CD62L) or ₄₇ integrin adhesion molecules mediating homing to lymphatic tissues. Accordingly, we observed a decrease in CD45RA⁺CCR7⁺ naive and CD45RA^–CCR7⁺ central memory T cells. Numbers of CD45RA^–CCR7^– memory effector and CD45RA⁺CCR7 terminally differentiated T cells, on the other hand, remained unchanged. No comparable changes were observed in the group of healthy volunteers. In conclusion, patients with solid tumors treated with WBH show an increase in NK and NK T cells. In a later phase, plasma concentrations of IL-8, hGH, and cortisol increase, correlated with an influx of neutrophils into the peripheral blood. The alterations in T-cell populations suggest that WBH may induce naive and central-memory T cells to enter lymphatic tissue to await antigen exposure and effector T cells to migrate into peripheral tissues to exert their effector function. Although the exercise group may not be an appropriate control to proof the effect of WBH, these changes were not seen in the healthy volunteers performing physical exercise.

immunotherapy; chemokine receptors; fever

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