Short-Term Fever-Range Hyperthermia Accelerates NETosis and Reduces Pro-inflammatory Cytokine Secretion by Human...

Area of Science:

• Immunology
• Cellular Biology
• Pathophysiology

Background:

• Fever is a common response to infection and inflammation.
• Fever-range hyperthermia (FRH) is known to enhance neutrophil recruitment.
• The specific impact of short FRH on neutrophil functions remains less understood.

Purpose of the Study:

• To investigate the effects of a brief period of fever-range hyperthermia (STFRH) on human neutrophil functions.
• To assess STFRH's influence on neutrophil apoptosis, NETosis, and cytokine production.

Main Methods:

• Human neutrophils were exposed to STFRH (1 hour at elevated temperature).
• Neutrophil apoptosis, NETosis (DNA decondensation, extracellular DNA-MPO complexes), reactive oxygen species (ROS), and autophagy were measured.
• Neutrophil responses to lipopolysaccharide (LPS), phorbol myristate acetate (PMA), and *Pseudomonas aeruginosa* were evaluated.

Main Results:

• STFRH did not affect spontaneous neutrophil apoptosis but reversed LPS-induced anti-apoptotic effects.
• STFRH accelerated PMA- and *P. aeruginosa*-induced NETosis, associated with increased ROS production.
• STFRH reduced pro-inflammatory cytokine (CXCL8/IL-8, IL-1β) release but did not impair bacterial killing capacity.

Conclusions:

• A short period of mild hyperthermia significantly modulates neutrophil functions.
• Fever spikes may induce an 'emergency' neutrophil response, promoting NET formation to contain bacteria.
• This response also serves to limit excessive inflammation by reducing pro-inflammatory cytokine release.