Practitioners may someday use heat therapy to reduce organ rejection in transplant patients, fight cancer and treat autoimmune problems, according to researchers from the University of Kentucky.
Healers have used thermotherapy to fight disease for thousands of years. From as far back as 500 BCE, Egyptian physicians would prescribe thermal baths, mud baths and hot air caverns to treat common diseases.
While these ancient healers could not know that heat could reduce organ rejection, they did realize that hyperthermic temperature changes could promote healing. In fact, Hippocrates once said, "Give me the power to produce fever, and I will cure all disease."
Trial and error has produced most of the information that modern practitioners know about heat therapy. Advancing medical technologies will allow researchers to apply increasingly detailed, real-time, hypothesis-driven methods to investigate the effects of temperature on organ transplants and diseases.
"It is apparent that high temperature is naturally involved in immune response. As we get sick we normally develop some level of fever, which is involved with the body's normal response to infections. This activates the immune system to attack or eliminate infections," said Mihail Mitov, Ph.D., lead author on the abstract in a press release.
"A popular theory in the field of thermotherapy is that prolonged hyperthermia causes cell-cycle arrest in cancer cells. This explains some of the cancer-stopping effects of thermotherapy. But apparently, there are also changes in the energy metabolism of cells and possibly other yet unknown processes that affect the energetic profiles of the cells. These processes could be exploited for the development of new treatments or therapeutic approaches with fewer side effects than chemotherapy."
To function properly, T cells and other immune cells rely on an activation process that involves breaking down glucose into pyruvate. This glycolysis changes T cell metabolism in ways that help bolster the cell's own ability to ward off infection and disease.
This study investigates how changes in temperature might affect mitochondrial function and glycolysis of three colorectal cancer cell lines and primary human T cells.
The research team led by Mihail Mitov, Ph.D., exposed T cells and colorectal cancer cells to temperatures that were higher and lower than normal body temperatures. The team then observed the effects of the hyper- and hypothermic temperature changes on the bioenergetics in both T cells and cancer cells.
Researchers at the University of Kentucky presented their findings at the American Physiological Society's Physiological Bioenergetics: Mitochondria from Bench to Bedside conference held Aug. 27-30 in San Diego.
The researchers used Seahorse XF96 technology that allowed them to measure glycolytic capacity, glycolytic reserve and nonglycolytic acidification in colorectal cancer cells and T cells. They analyzed glycolysis in cells at 32, 37 and 42 degrees Celsius. The scientists discovered that temperature significantly changed multiple components of the glycolytic process in each of the cell types.
"We found that short-term hyperthermia (a 2.5-hour exposure) increases glycolysis of T cells, thus putting them in an active state that potentially is ready to fight cancer or infections," Mitov noted.
However, if the exposure to hyperthermia is prolonged, the T cells become inactive, which could be beneficial for people who need a suppressed immune response, such as those with an organ transplant or autoimmune diseases. Effector CD8 T cells play a major role in allograft rejection.
"These findings provide valuable insights into the metabolic and bioenergetics changes of colorectal cancer cells and human T cells under hypo- and hyperthermia conditions that could potentially lead to the development of better-targeted and personalized strategies for patients with cancer, metabolic disorders, diabetes or transplanted organs," the research team wrote.
