Fever temperatures can have a significant impact on immune cell metabolism, proliferation, and activity, as discovered by researchers at Vanderbilt University Medical Center. The study, published in Science Immunology, found that in a subset of T cells, fever temperatures can lead to mitochondrial stress, DNA damage, and cell death. This understanding of how cells respond to heat could also shed light on how chronic inflammation can contribute to cancer development. Despite the importance of this area of research, it remains relatively understudied compared to other temperature-related fields such as agriculture.
The study was led by Jeff Rathmell, a professor of Immunobiology at Vanderbilt University, who highlighted the lack of exploration into the effects of temperature on inflammatory processes. Most cells in laboratory settings are cultured at standard body temperature, making it challenging to investigate the impact of varying temperatures. Graduate student Darren Heintzman, whose father had an autoimmune disease with a constant fever, decided to study the effects of fever temperatures on immune cells. He found that increased temperature enhanced helper T cell activity while reducing regulatory T cell suppressive capacity.
However, an unexpected discovery was made during the study: a subset of helper T cells, known as Th1 cells, underwent mitochondrial stress, DNA damage, and cell death in response to fever temperatures. This finding was surprising as Th1 cells play a crucial role in fighting infections, including those that cause fevers. The researchers observed that while some Th1 cells died due to the stress, others adapted, changed their mitochondria, and became more resilient to stress. These surviving cells demonstrated increased proliferation and cytokine production, enhancing their immune response.
Through further investigation, Heintzman uncovered the molecular events that occur in T cells in response to fever temperatures. Heat led to the impairment of a mitochondrial protein complex, ETC1, which triggered DNA damage and activated p53, a tumor suppressor protein. Th1 cells were found to be more sensitive to ETC1 impairment compared to other T cell subtypes. The researchers also discovered similar changes in sequencing databases for samples from patients with Crohn’s disease and rheumatoid arthritis, supporting the defined molecular signaling pathway.
The study suggests that heat can be mutagenic when cells respond with mitochondrial stress and fail to repair DNA damage or undergo cell death. Chronic inflammation with elevated tissue temperatures could explain how cells become tumorigenic, potentially contributing to the development of cancer. It is estimated that up to 25% of cancers are linked to chronic inflammation. Overall, the research provides insight into the mechanisms behind the effects of fever temperatures on immune cells and how they can impact health outcomes. The findings have significant implications for understanding the role of fever in the immune response and in chronic inflammatory conditions.