Fever temperatures rev up immune cell metabolism, proliferation and activity, but they also — in a particular subset of T cells — cause mitochondrial stress, DNA damage and cell death, Vanderbilt University Medical Center researchers have discovered.

The findings, published Sept. 20 in the journal Science Immunology, offer a mechanistic understanding for how cells respond to heat and could explain how chronic inflammation contributes to the development of cancer.

The impact of fever temperatures on cells is a relatively understudied area, said Jeff Rathmell, PhD, Cornelius Vanderbilt Professor of Immunobiology and corresponding author of the new study. Most of the existing temperature-related research relates to agriculture and how extreme temperatures impact crops and livestock, he noted. It’s challenging to change the temperature of animal models without causing stress, and cells in the laboratory are generally cultured in incubators that are set at human body temperature: 37 degrees Celsius (98.6 degrees Fahrenheit).

Researchers from the Sapienza University of Rome found that caffeine has a positive effect on endothelial cells, a group of cells responsible for vascular regeneration.

We studied the role of caffeine intake on endothelial function in SLE by assessing its effect on circulating endothelial progenitor cells (EPCs) both ex vivo in SLE patients and in vitro in healthy donors (HD) treated with SLE sera.

Methods.

We enrolled SLE patients without traditional cardiovascular risks factors. Caffeine intake was evaluated with a 7-day food frequency questionnaire. EPCs percentage was assessed by flow cytometry analysis and, subsequently, EPCs pooled from six HD were co-cultured with caffeine with and without SLE sera. After 7 days, we evaluated cells’ morphology and ability to form colonies, the percentage of apoptotic cells by flow cytometry analysis and the levels of autophagy and apoptotic markers by western blot. Finally, we performed a western blot analysis to assess the A2AR/SIRT3/AMPK pathway.