Response to systemic endotoxemia among humans bearing polymorphisms of the Toll-like receptor 4 (hTLR4).
Mutations (Asp299Gly and Thr399Ile) in the human Toll-like receptor 4 (hTLR4) gene are reportedly associated with hyporesponsiveness to inhaled LPS in humans. It was hypothesized that normal volunteers with these hTLR4 mutations would manifest altered physiological responses to intravenous LPS administration. Human subjects (n = 57) were administered LPS (2 ng/kg) intravenously and monitored for vital signs (temperature, heart rate, mean arterial pressure). Blood-derived genomic DNA samples were evaluated using PCR to detect hTLR4 and TLR2 mutations. Heterozygous hTLR4 mutations were identified in 8 of the 57 subjects studied. Subjects with hTLR4 mutations demonstrated similar responses to LPS administration. The moderate systemic inflammatory response produced by intravenous LPS administration in human subjects is not modulated by the presence of heterozygous mutations in the hTLR4 gene.
Calvano
Jacqueline E
JE
Division of Surgical Sciences, Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, CAB 7300, 125 Paterson Street, New Brunswick, NJ 08903, USA.
Bowers
Daniel J
DJ
Coyle
Susette M
SM
Macor
Marie
M
Reddell
Michael T
MT
Kumar
Ashwini
A
Calvano
Steve E
SE
Lowry
Stephen F
SF
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004198:Disease Susceptibility; D019446:Endotoxemia / Q000097:blood / Q000235:genetics*; D004731:Endotoxins / Q000008:administration & dosage*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000502:physiology; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D013696:Temperature; D051197:Toll-Like Receptor 4 / Q000097:blood / Q000235:genetics*
D004731:Endotoxins; D015850:Interleukin-6; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4