Cutting Edge: Fever-Associated Temperatures Enhance Neutrophil Responses to Lipopolysaccharide: A Potential Mechanism Involving Cell Metabolism

• Published in: The Journal of immunology (1950) Vol. 169; no. 10; pp. 5396 - 5400
• Main Authors: Rosenspire, Allen J, Kindzelskii, Andrei L, Petty, Howard R
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-11-2002
• Subjects: Body Temperature - immunology; Cell Adhesion - immunology; Extracellular Space - immunology; Extracellular Space - metabolism; Fever - immunology; Fever - metabolism; Humans; Lipopolysaccharides - immunology; Microscopy, Fluorescence; NADP - metabolism; Neutrophil Activation - immunology; Neutrophils - immunology; Neutrophils - metabolism; Nitric Oxide - biosynthesis; Reactive Nitrogen Species - biosynthesis; Reactive Oxygen Species - metabolism; Superoxides - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.10.5396

Although much progress has been made in elucidating the mechanisms underlying the physiological regulation of fever, there is little understanding of the biological utility of fever's thermal component. Considering the evolutionary co-conservation of fever and innate immunity, we hypothesize that fever's thermal component might in general augment innate immune function and, in particular, neutrophil activation. Accordingly, we have evaluated the effect of febrile temperatures on neutrophil function at the single-cell level. We find that reactive oxygen intermediates and NO release are greatly enhanced at febrile temperatures for unstimulated as well as LPS-stimulated adherent human neutrophils. Furthermore, our studies suggest that these changes in oxidant release are linked to upstream changes in NADPH dynamics. Inasmuch as reactive oxygen intermediates and NO production are important elements in innate immune responses to bacterial pathogens, we suggest that the febrile rise in core temperature is a broad-based systemic signaling mechanism to enhance innate immunity.