Fever-range whole-body heat treatment stimulates antigen-specific T-cell responses in humans.

Increase in body temperature has been thought to play an important role in the regulation of immune responses, although its precise mechanisms are still under investigation. Here, we examined the effects of physiologically relevant thermal stress on the cytokine production from human peripheral T cells. Volunteers were heated using a whole-body hyperthermia device, the rectal temperature was maintained above 38.5 °C for more than 60 min, and peripheral blood mononuclear cells (PBMCs) were obtained before and after the treatment. When T cells were stimulated with anti-CD3/CD28 antibodies, marked increases in the production of interferon-γ (IFN-γ) and interleukin-2 were observed in PBMCs prepared immediately after and 24h after the treatment. Similarly, enhanced production of IFN-γ in response to the tuberculin purified protein derivative or antigenic viral peptides was also observed immediately after and 24h after the treatment. Fluorescence photo-bleaching analyses showed heat-induced increase of membrane fluidity in T cells, which probably enables them to induce rapid and efficient cluster formation of molecules involved in antigen recognition and signal transduction for T-cell stimulation. We concluded that physiologically relevant thermal stress could efficiently modify T-cell responsiveness to various stimuli, including enhanced responses to specific antigens.

Changes in plasma alpha and gamma tocopherol levels before and after long-term local hyperthermia in cancer patients.

Local hyperthermia is one of the heat therapies for cancer patients. The effect of this therapy is recognized to affect the immune function. On the other hand, researchers have recently suggested that vitamin E has not only antioxidant but also other functions including the immune function. However, the association between local hyperthermia therapy and vitamin E level is not yet well understood. Comparing plasma alpha and gamma tocopherol levels before and after the therapy, the basal levels of both tocopherols in the cancer patients did not significantly differ from those in healthy subjects. However, the interindividual difference in the basal levels was very wide in the cancer patients. After long-term local hyperthermia (more than 70 days), the levels of both tocopherols were significantly higher than the basal levels. This result suggests that long-term local hyperthermia therapy influences plasma tocopherol level in cancer patients; thus, an increase in vitamin E level may play an important role in the therapy of cancer patients.

Immune-related effects of local hyperthermia in patients with primary liver cancer.

BACKGROUND/AIMS: To investigate immune-related effects of local hyperthermia (HT) with hepatocellular carcinoma (HCC). METHODOLOGY: Immune status after 7 HT was studied in 11 patients (M/F - 9/2; 1st group). The effects were also evaluated during one HT session in 4 of those pts (M/F - 4/0; 2nd group). The HT treatment was performed by means of an 8-MHz capacitive heating device, Thermotron RF8 (Japan). The mean time of one HT session was 60 min, HT was performed 1-2 times a week. In both groups the percentage of T and B cells, CD4+, CD8+ subsets of T cells, the CD4/CD8 ratio and activation of NK cells were evaluated. RESULTS: In the 1st group, CD4/CD8 ratio was decreased significantly (p < 0.05), whereas the relative amount of CD4+ T cells showed a tendency to decrease (p=0.063), and CD8--to increase (p=0.088). An activation of NK cells was observed in patients who had a low or normal pretreatment level of activation. In the 2nd group, there was a significant decrease in the CD4/CD8 ratio by the end of the treatment (p < 0.05) and increased activity of NK cells as early as 20 min after the onset of HT (p < 0.05). CONCLUSIONS: Our results suggest that HT stimulates the immunity of cancer patients by several means and therefore may exhibit indirect anticancer effect. In addition, activation of NK cells by HT may be associated with improved quality of life.

Successful treatment of hepatocellular carcinoma with percutaneous ethanol injection therapy and local hyperthermia.

The patient K.I., a 72-year-old male, was admitted to Nishide Hospital in July 1999 for hemodialysis treatment of end-stage chronic renal failure. At the time of his admission, an ultrasound examination of the patient's liver revealed a large mass in the S5-S8 segment. A hepatocellular carcinoma was suspected from the characteristic mosaic pattern seen with ultrasound and the elevation of alpha-fetoprotein in the serum. The patient's condition was considered to be medically inoperable, due to the patient's adaptation to hemodialysis. Furthermore, transcatheter arterial embolization was not indicated due to the patient's history of hypersensitivity to roentgen-contrast materials. An attempt to palliate the malignancy was made with a combination of local hyperthermia and percutaneous ethanol injection therapy. Magnetic resonance imaging revealed that the tumor structure had changed after 10 days of percutaneous ethanol injection therapy and that 2 months later the tumor size had decreased by about 50%. Moreover, the alpha-fetoprotein level had returned to normal by that time. In addition, this treatment did not cause any disturbance in the liver function. The patient tolerated treatment well. A combined treatment of local hyperthermia with percutaneous ethanol injection therapy appears to be useful in the management of hepatocellular carcinomas, especially in cases in which more aggressive treatment is not acceptable.