Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 289, Issue 2, Pages R348-R352Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00223.2005
Keywords
body temperature; fever; hypothermia; inflammation; Toll-like receptors; TLR2; TLR4; LPS
Categories
Funding
- NINDS NIH HHS [R01 NS 41233] Funding Source: Medline
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LPS preparations cause a variety of body temperature (T-b) responses: monophasic fever, different phases of polyphasic fever, and hypothermia. Conventional (c) LPS preparations contain highly active lipoprotein contaminants (endotoxin proteins). Whereas LPS signals predominantly via the Toll-like receptor (TLR) 4, endotoxin proteins signal via TLR2. Several TLR2-dependent responses of immunocytes to cLPS in vitro are triggered by endotoxin proteins and not by LPS itself. We tested whether any T-b response to cLPS from Escherichia coli 055:B5 is triggered by non-TLR4-signaling contaminants. A decontaminated (d) LPS preparation (free of endotoxin proteins) was produced by subjecting cLPS to phenol-water reextraction. The presence of non-TLR4-signaling contaminants in cLPS (and their absence in dLPS) was confirmed by showing that cLPS (but not dLPS) induced IL-1 beta expression in the spleen and increased serum levels of TNF-alpha and IL-1 beta of C3H/HeJ mice; these mice bear a nonfunctional TLR4. Yet, both cLPS and dLPS caused cytokine responses in C3H/HeOuJ mice; these mice bear a fully functional TLR4. We then studied the T-b responses to cLPS and dLPS in Wistar rats preimplanted with jugular catheters. At a neutral ambient temperature (30 degrees C), a low (0.1 mu g/kg iv) dose of cLPS caused a monophasic fever, whereas a moderate ( 10 mu g/kg iv) dose produced a polyphasic fever. In the cold (20 degrees C), a high (500 mu g/kg iv) dose of cLPS caused hypothermia. All T-b responses to dLPS were identical to those of cLPS. We conclude that all known T-b responses to LPS preparations are triggered by LPS per se and not by non-TLR4-signaling contaminants of such preparations.
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