0 19 Temperature-induced temperature-induced JJ 20 35 down-regulation down-regulation NN 36 38 of of IN 39 42 the the DT 43 57 glucocorticoid glucocorticoid NN 58 66 receptor receptor NN 67 69 in in IN 70 80 peripheral peripheral JJ 81 86 blood blood NN 87 98 mononuclear mononuclear JJ 99 108 leucocyte leucocyte NN 109 111 in in IN 112 120 patients patient NNS 121 125 with with IN 126 132 sepsis sepsis NN 133 135 or or CC 136 142 septic septic JJ 143 148 shock shock NN 148 149 . . . 151 160 OBJECTIVE objective NN 160 161 : : : 162 172 Activation Activation NNP 173 175 of of IN 176 179 the the DT 180 210 hypothalamic-pituitary-adrenal hypothalamic-pituitary-adrenal JJ 211 215 axis axis NN 216 218 is be VBZ 219 221 of of IN 222 227 vital vital JJ 228 238 importance importance NN 239 245 during during IN 246 254 critical critical JJ 255 262 illness illness NN 262 263 . . . 264 266 We we PRP 267 271 have have VBP 272 279 studied study VBN 280 283 the the DT 284 292 adaptive adaptive JJ 293 303 mechanisms mechanism NNS 304 309 which which WDT 310 315 occur occur VBP 316 318 at at IN 319 322 the the DT 323 328 level level NN 329 331 of of IN 332 335 the the DT 336 350 glucocorticoid glucocorticoid NN 351 359 receptor receptor NN 360 362 in in IN 363 377 glucocorticoid glucocorticoid NN 378 384 target target NN 385 392 tissues tissue NNS 393 395 in in IN 396 404 patients patient NNS 405 409 with with IN 410 416 sepsis sepsis NN 417 419 or or CC 420 426 septic septic JJ 427 432 shock shock NN 432 433 . . . 434 440 DESIGN design NN 440 441 : : : 442 445 The the DT 446 453 effects effect NNS 454 456 of of IN 457 475 hypercortisolaemia hypercortisolaemia NN 475 476 , , , 477 489 hyperthermia hyperthermia NN 490 493 and and CC 494 502 cellular cellular JJ 503 514 composition composition NN 515 517 on on IN 518 524 number number NN 525 527 of of IN 528 542 glucocorticoid glucocorticoid NN 543 552 receptors receptor NNS 553 556 per per IN 557 561 cell cell NN 562 565 and and CC 566 571 their their PRP$ 572 580 affinity affinity NN 581 585 were be VBD 586 595 evaluated evaluate VBN 595 596 , , , 597 601 both both CC 602 604 in in FW 605 610 vitro vitro FW 611 614 and and CC 615 617 in in FW 618 622 vivo vivo FW 622 623 , , , 624 626 in in IN 627 637 peripheral peripheral JJ 638 643 blood blood NN 644 655 mononuclear mononuclear JJ 656 666 leucocytes leucocyte NNS 667 669 of of IN 670 677 control control NN 678 686 subjects subject NNS 687 690 and and CC 691 693 in in IN 694 702 patients patient NNS 703 707 with with IN 708 714 sepsis sepsis NN 715 717 or or CC 718 724 septic septic JJ 725 730 shock shock NN 730 731 . . . 732 740 SUBJECTS subjects NNS 740 741 : : : 742 749 Fifteen fifteen CD 750 758 patients patient NNS 759 760 ( ( ( 760 763 age age NN 764 769 25-79 25-79 CD 769 770 ) ) ) 771 775 with with IN 776 782 sepsis sepsis NN 783 785 or or CC 786 792 septic septic JJ 793 798 shock shock NN 799 802 who who WP 803 807 were be VBD 808 816 admitted admit VBN 817 819 to to TO 820 822 an an DT 823 832 intensive intensive JJ 833 837 care care NN 838 842 unit unit NN 843 847 were be VBD 848 855 studied study VBN 855 856 . . . 857 860 The the DT 861 868 control control NN 869 874 group group NN 875 884 consisted consist VBD 885 887 of of IN 888 890 24 24 CD 891 898 healthy healthy JJ 899 909 laboratory laboratory NN 910 919 employees employee NNS 919 920 . . . 921 933 MEASUREMENTS measurements NNS 933 934 : : : 935 938 The the DT 939 946 binding binding NN 947 955 capacity capacity NN 956 959 and and CC 960 968 affinity affinity NN 969 971 of of IN 972 975 the the DT 976 990 glucocorticoid glucocorticoid NN 991 1000 receptors receptor NNS 1001 1005 were be VBD 1006 1014 measured measure VBN 1015 1018 and and CC 1019 1027 compared compare VBN 1028 1030 to to TO 1031 1039 clinical clinical JJ 1040 1044 data datum NNS 1045 1048 and and CC 1049 1052 the the DT 1053 1059 plasma plasma NN 1060 1068 cortisol cortisol NN 1069 1083 concentrations concentration NNS 1083 1084 . . . 1085 1092 RESULTS results NNS 1092 1093 : : : 1094 1112 Hypercortisolaemia Hypercortisolaemia NNP 1112 1113 , , , 1114 1116 in in FW 1117 1122 vitro vitro FW 1122 1123 , , , 1124 1132 resulted result VBD 1133 1135 in in IN 1136 1137 a a DT 1138 1147 decreased decrease VBN 1148 1156 affinity affinity NN 1157 1160 and and CC 1161 1162 a a DT 1163 1172 decreased decrease VBN 1173 1180 binding binding NN 1181 1189 capacity capacity NN 1190 1192 of of IN 1193 1196 the the DT 1197 1211 glucocorticoid glucocorticoid NN 1212 1220 receptor receptor NN 1220 1221 . . . 1222 1224 In in FW 1225 1230 vitro vitro FW 1230 1231 , , , 1232 1244 hyperthermia hyperthermia NN 1245 1247 as as RB 1248 1252 well well RB 1253 1255 as as IN 1256 1266 variations variation NNS 1267 1269 in in IN 1270 1273 the the DT 1274 1282 cellular cellular JJ 1283 1294 composition composition NN 1295 1298 did do VBD 1299 1302 not not RB 1303 1312 influence influence VB 1313 1316 the the DT 1317 1331 glucocorticoid glucocorticoid NN 1332 1340 receptor receptor NN 1340 1341 . . . 1342 1344 In in FW 1345 1349 vivo vivo FW 1349 1350 , , , 1351 1356 there there EX 1357 1360 was be VBD 1361 1363 no no DT 1364 1370 change change NN 1371 1373 in in IN 1374 1377 the the DT 1378 1384 number number NN 1385 1387 of of IN 1388 1397 receptors receptor NNS 1398 1401 per per IN 1402 1406 cell cell NN 1407 1409 in in IN 1410 1418 patients patient NNS 1419 1423 with with IN 1424 1430 sepsis sepsis NN 1431 1433 or or CC 1434 1440 septic septic JJ 1441 1446 shock shock NN 1447 1449 as as IN 1450 1458 compared compare VBN 1459 1461 to to TO 1462 1469 healthy healthy JJ 1470 1478 controls control NNS 1478 1479 . . . 1480 1487 However however RB 1487 1488 , , , 1489 1490 a a DT 1491 1500 decreased decrease VBN 1501 1509 affinity affinity NN 1510 1512 of of IN 1513 1516 the the DT 1517 1531 glucocorticoid glucocorticoid NN 1532 1540 receptor receptor NN 1541 1544 was be VBD 1545 1553 observed observe VBN 1553 1554 . . . 1555 1560 There there EX 1561 1564 was be VBD 1565 1566 a a DT 1567 1571 weak weak JJ 1572 1575 but but CC 1576 1587 significant significant JJ 1588 1596 negative negative JJ 1597 1608 correlation correlation NN 1609 1616 between between IN 1617 1621 body body NN 1622 1633 temperature temperature NN 1634 1637 and and CC 1638 1641 the the DT 1642 1648 number number NN 1649 1651 of of IN 1652 1666 glucocorticoid glucocorticoid NN 1667 1676 receptors receptor NNS 1677 1679 in in IN 1680 1683 the the DT 1684 1691 patient patient NN 1692 1697 group group NN 1697 1698 . . . 1699 1704 There there EX 1705 1708 was be VBD 1709 1711 no no DT 1712 1720 relation relation NN 1721 1728 between between IN 1729 1740 circulating circulate VBG 1741 1749 cortisol cortisol NN 1750 1764 concentrations concentration NNS 1765 1768 and and CC 1769 1783 glucocorticoid glucocorticoid NN 1784 1792 receptor receptor NN 1793 1801 affinity affinity NN 1802 1805 and and CC 1806 1812 number number NN 1812 1813 . . . 1814 1825 CONCLUSIONS conclusions NNS 1825 1826 : : : 1827 1832 There there EX 1833 1835 is be VBZ 1836 1838 no no DT 1839 1846 obvious obvious JJ 1847 1857 regulation regulation NN 1858 1860 of of IN 1861 1864 the the DT 1865 1871 number number NN 1872 1874 of of IN 1875 1889 glucocorticoid glucocorticoid NN 1890 1899 receptors receptor NNS 1900 1902 by by IN 1903 1909 plasma plasma NN 1910 1918 cortisol cortisol NN 1919 1933 concentrations concentration NNS 1934 1936 in in FW 1937 1941 vivo vivo FW 1941 1942 . . . 1943 1946 The the DT 1947 1956 decreased decrease VBN 1957 1965 affinity affinity NN 1966 1968 of of IN 1969 1972 the the DT 1973 1987 glucocorticoid glucocorticoid NN 1988 1996 receptor receptor NN 1997 2005 together together RB 2006 2010 with with IN 2011 2014 the the DT 2015 2023 negative negative JJ 2024 2035 correlation correlation NN 2036 2043 between between IN 2044 2056 hyperthermia hyperthermia NN 2057 2060 and and CC 2061 2064 the the DT 2065 2071 number number NN 2072 2074 of of IN 2075 2089 glucocorticoid glucocorticoid NN 2090 2099 receptors receptor NNS 2100 2102 in in IN 2103 2111 patients patient NNS 2112 2116 with with IN 2117 2123 sepsis sepsis NN 2124 2126 or or CC 2127 2133 septic septic JJ 2134 2139 shock shock NN 2140 2147 suggest suggest VBP 2148 2152 that that IN 2153 2183 hypothalamic-pituitary-adrenal hypothalamic-pituitary-adrenal JJ 2184 2188 axis axis NN 2189 2199 activation activation NN 2200 2206 during during IN 2207 2215 critical critical JJ 2216 2223 illness illness NN 2224 2226 is be VBZ 2227 2238 accompanied accompany VBN 2239 2241 by by IN 2242 2252 peripheral peripheral JJ 2253 2263 adaptation adaptation NN 2264 2266 in in IN 2267 2281 glucocorticoid glucocorticoid NN 2282 2290 receptor receptor NN 2291 2297 number number NN 2298 2301 and and CC 2302 2310 affinity affinity NN 2310 2311 . . .