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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4000-4002.
Prepublished online as a Blood First Edition Paper on January 10, 2006; DOI 10.1182/blood-2005-11-4743.
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IMMUNOBIOLOGY
Brief report
Bacterial lipopolysaccharide fever is initiated via Toll-like receptor 4 on hematopoietic cells
Alexandre A. Steiner,
Sumana Chakravarty,
Alla Y. Rudaya,
Miles Herkenham, and
Andrej A. Romanovsky
From the Systemic Inflammation Laboratory, Trauma Research, St Joseph's Hospital and Medical Center, Phoenix, AZ; and Section on Functional Neuroanatomy, National Institute of Mental Health, National Institutes of Health, Bethesda, MD.
Lipopolysaccharide (LPS), a well-known bacterial pyrogen, is recognized by several receptors, including the Toll-like receptor 4 (TLR4), on various cells. Which of these receptors and cells are linked to fever production is unknown. By constructing 4 mouse chimeras and studying their thermoregulatory responses, we found that all 3 phases of the typical LPS fever depend on TLR4 signaling. The first phase is triggered via the TLR4 on hematopoietic cells. The second and third phases involve TLR4 signaling in both hematopoietic and nonhematopoietic cells.
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