Author/Authors :
Calvano، نويسنده , , Jacqueline E. and Bowers، نويسنده , , Daniel J. and Coyle، نويسنده , , Susette M. and Macor، نويسنده , , Marie and Reddell، نويسنده , , Michael T. and Kumar، نويسنده , , Ashwini and Calvano، نويسنده , , Steve E. and Lowry، نويسنده , , Stephen F.، نويسنده ,
Abstract :
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.
