Have you ever wondered how fever temperatures impact your immune cells? Well, researchers at Vanderbilt University Medical Center have uncovered some fascinating insights into this relatively understudied area. In a recent study published in the journal Science Immunology, they revealed how fever temperatures can rev up immune cell metabolism, proliferation, and activity.
However, the researchers also found that in a specific subset of T cells, fever temperatures can lead to mitochondrial stress, DNA damage, and cell death. This discovery could provide a better understanding of how cells respond to heat and how chronic inflammation may contribute to the development of cancer.
The lead researcher, Jeff Rathmell, explained that this area of temperature-related research is often overlooked, with most studies focusing on how extreme temperatures impact agriculture. It’s challenging to study the effects of fever temperatures on cells because animal models are typically kept at standard body temperature, and cells in the lab are cultured at 37 degrees Celsius.
Graduate student Darren Heintzman was particularly interested in this topic due to personal reasons, as his father had experienced a prolonged fever due to an autoimmune disease. This inspired Heintzman to investigate the effects of fever temperatures on immune system T cells.
Heintzman’s experiments revealed that increasing the temperature to 39 degrees Celsius enhanced helper T cell metabolism, proliferation, and inflammatory activity, while reducing regulatory T cell suppressive capacity. This heightened immune response is beneficial during infections, as it allows the body to combat pathogens more effectively.
However, the researchers were surprised to discover that Th1 cells, a subset of helper T cells crucial for fighting infections, experienced mitochondrial stress, DNA damage, and cell death under fever conditions. Despite this initial setback, some Th1 cells adapted to the stress, becoming more resistant and efficient at producing immune signaling molecules.
Heintzman’s molecular analysis revealed that fever temperatures impaired a mitochondrial protein complex called ETC1, which triggered DNA damage and activated the tumor suppressor protein p53. This response was more pronounced in Th1 cells compared to other T cell subtypes.
Further exploration of sequencing databases showed similar changes in Th1 cells from patients with inflammatory diseases like Crohn’s and rheumatoid arthritis, highlighting the clinical relevance of these findings.
Rathmell emphasized that understanding how cells respond to stress, such as elevated temperatures, is crucial. Changes in cellular metabolism due to ETC1 impairment could have significant implications for various tissues and disease states.
Moreover, the researchers believe that prolonged exposure to fever temperatures and chronic inflammation could lead to mutagenic effects, potentially contributing to the development of cancer. Approximately 25% of cancers are linked to chronic inflammation, underscoring the importance of this research.
In conclusion, Rathmell stated that while a mild fever can be beneficial for combating infections, prolonged and severe fevers can have detrimental effects on the immune system. By unraveling the mechanisms behind these responses, the researchers hope to shed light on how fever temperatures impact immune cell function and disease processes.
The study was supported by various grants from the National Institutes of Health, the Lupus Research Alliance, the Waddell Walker Hancock Cancer Discovery Fund, and the National Science Foundation.
