Induced hyperthermia causes significant changes in lymphocytes

Background

Changes in lymphocyte subpopulations are determined under several clinical conditions eg during activation of the immune system. Our aim was to analyze the influence of induced elevated body temperatures on lymphocytes in patients without infections or other physiological stimulators of the immune system. Therefore we examined blood of patients with metastatic colorectal carcinoma during whole body hyperthermia of 42°C caused by infrared-A-radiation. This is used as part of so called `systemische Krebs-Mehrschritt-Therapie' (sKMT), which was started as a phase I/II clinical study at Virchow-Klinikum in 1997.

Methods

Lymphocyte subpopulations were investigated by flow-cytometry-analysis. Blood samples were obtained before beginning of therapy at 37°C, at 40°C, at the end of the plateau of 42°C and after therapy at 37°C again. Time between investigations was about 2 h. Subpopulations were natural killer cells, T-Cells, IL2-Receptor on T-Cells, T4-Cells and T8-Cells. Cell counts were compared by using a Wilcoxon rank sum test.

Results

The number of lymphocytes per nl decreased significantly from 37°C to 42°C (Fig. 1). This effect was mainly caused by a significant decrease of the absolute T4-Cell count and a slight decrease of the T8-Cell count with a resulting significant decrease of T-Cells. In addition, IL2-Receptor expression on T-Cells, as a marker for activation, decreased significantly. In contrast, the number of natural killer cells per nl increased. Looking for changes in relation between lymphocyte subpopulations, we found a significant percentual decrease of T4-Cells (Fig. 2), no percentual changes in T8-Cells but a significant percentual increase of natural killer cells (Fig. 3). Effects were reversible and at the last time-point at 37°C all examined parameters showed a tendency to the initial values.

Conclusions

Elevated body temperatures up to 42°C induce a change in lymphocytes which is similar to early responses of the immune system to other stress situations or host response. For example natural killer cells are known to increase in the early phase after severe trauma, whereas the number of T4-Cells decreases in these patients. Thus, isolated induced hyperthermia in absence of infections or other physiological stimulators of the immune system seems to cause a kind of host response. It seems remarkable, that these effects were reversible in a very short time-period after decrease of temperature.

Fig. 1-3