Fever Boosts Immune Defense by Activating Antimicrobial Peptides While Protecting Cells

The fever response is a fundamental physiological reaction triggered during infection and inflammation. It's a hallmark of the body's fight against pathogens, yet the precise importance of this elevated temperature for the function of the body's natural antimicrobial peptides (AMPs), like LL-37, and its balance with potential cellular damage, has remained largely unknown.

The study revealed that the activity of human AMP LL-37 is significantly temperature-dependent, with its antibacterial efficacy increasing at higher temperatures. This temperature sensitivity was not an accidental enzymatic property; AMPs from animals with different body temperatures exhibited distinct optimal temperature ranges. This suggests an evolutionary adaptation. The most critical finding was that AMP temperature sensitivities are generally tuned to an animal's body temperature, and for animals capable of inducing fever, this mechanism is actively used to increase AMP's antibacterial efficacy against bacteria. Crucially, this enhanced killing was achieved while simultaneously limiting mitochondrial damage in the host cells when pathogens were absent, indicating a careful evolutionary balance. In contrast, cold-blooded animals, unable to induce fever, employ alternative strategies to avoid mitochondrial damage.