0 14 Glucocorticoid glucocorticoid NN 15 24 receptors receptor NNS 25 28 are be VBP 29 43 down-regulated down-regulate VBN 44 46 in in IN 47 55 inflamed inflamed JJ 56 63 colonic colonic JJ 64 70 mucosa mucosa NN 71 74 but but CC 75 78 not not RB 79 81 in in IN 82 92 peripheral peripheral JJ 93 98 blood blood NN 99 110 mononuclear mononuclear JJ 111 116 cells cell NNS 117 121 from from IN 122 130 patients patient NNS 131 135 with with IN 136 148 inflammatory inflammatory JJ 149 154 bowel bowel NN 155 162 disease disease NN 163 164 [ [ ( 164 167 see see VB 168 176 comments comment NNS 176 177 ] ] ) 179 189 BACKGROUND BACKGROUND NNP 189 190 : : : 191 198 Growing grow VBG 199 207 evidence evidence NN 208 217 indicates indicate VBZ 218 222 that that IN 223 226 the the DT 227 233 immune immune JJ 234 240 system system NN 241 244 and and CC 245 248 the the DT 249 279 hypothalamic-pituitary-adrenal hypothalamic-pituitary-adrenal JJ 280 286 system system NN 287 290 are be VBP 291 297 linked link VBN 298 300 by by IN 301 308 several several JJ 309 319 mechanisms mechanism NNS 319 320 , , , 321 324 for for IN 325 332 example example NN 333 346 intracellular intracellular JJ 347 361 glucocorticoid glucocorticoid NN 362 371 receptors receptor NNS 372 373 ( ( ( 373 376 hGR hGR NNP 376 377 ) ) ) 377 378 . . . 379 394 Glucocorticoids glucocorticoid NNS 395 398 are be VBP 399 402 the the DT 403 411 standard standard JJ 412 421 treatment treatment NN 422 424 of of IN 425 430 acute acute JJ 431 438 attacks attack NNS 439 441 of of IN 442 454 inflammatory inflammatory JJ 455 460 bowel bowel NN 461 468 disease disease NN 469 470 ( ( ( 470 473 IBD IBD NNP 473 474 ) ) ) 474 475 . . . 476 483 Binding binding NN 484 486 of of IN 487 502 glucocorticoids glucocorticoid NNS 503 505 to to TO 506 509 hGR hGR NNP 510 524 down-regulates down-regulate VBZ 525 528 the the DT 529 542 transcription transcription NN 543 545 of of IN 546 558 inflammatory inflammatory JJ 559 564 genes gene NNS 565 569 that that WDT 570 573 can can MD 574 583 propagate propagate VB 584 587 IBD ibd NN 587 588 . . . 589 597 PATIENTS patients NNS 598 601 AND and CC 602 609 METHODS methods NNS 609 610 : : : 611 614 IBD IBD NNP 615 623 patients patient NNS 624 628 were be VBD 629 635 either either RB 636 643 treated treat VBN 644 648 with with IN 649 653 5-60 5-60 CD 654 656 mg mg NN 657 659 of of IN 660 672 prednisolone prednisolone NN 673 676 for for IN 677 681 more more JJR 682 686 than than IN 687 688 1 1 CD 689 693 week week NN 694 696 or or CC 697 701 were be VBD 702 709 without without IN 710 724 glucocorticoid glucocorticoid NN 725 734 treatment treatment NN 735 738 for for IN 739 743 more more JJR 744 748 than than IN 749 750 4 4 CD 751 757 weeks. weeks. NN 758 761 hGR hGR NNP 762 768 levels level NNS 769 773 were be VBD 774 784 determined determine VBN 785 789 from from IN 790 798 isolated isolate VBN 799 806 cytosol cytosol NN 807 809 of of IN 810 820 peripheral peripheral JJ 821 826 blood blood NN 827 838 mononuclear mononuclear JJ 839 844 cells cell NNS 845 846 ( ( ( 846 851 PBMCs PBMC NNPS 851 852 ) ) ) 853 855 or or CC 856 863 mucosal mucosal JJ 864 872 biopsies biopsy NNS 873 878 using use VBG 879 880 a a DT 881 891 radioassay radioassay NN 892 896 with with IN 897 898 [ [ ( 898 915 3H]-dexamethasone 3H]-dexamethasone NNP 915 916 . . . 917 928 Interleukin Interleukin NNP 929 930 ( ( ( 930 932 IL IL NNP 932 933 ) ) ) 934 935 6 6 CD 936 942 levels level NNS 943 947 were be VBD 948 958 determined determine VBN 959 961 by by IN 962 975 enzyme-linked enzyme-linked JJ 976 989 immunosorbent immunosorbent JJ 990 995 assay assay NN 996 997 ( ( ( 997 1004 ELISA). ELISA). NNP 1005 1012 RESULTS RESULTS NNP 1012 1013 : : : 1014 1017 The the DT 1018 1026 systemic systemic JJ 1027 1028 ( ( ( 1028 1032 PBMC PBMC NNP 1032 1033 ) ) ) 1034 1037 hGR hGR NNP 1038 1044 levels level NNS 1045 1047 of of IN 1048 1070 corticosteroid-treated corticosteroid-treated JJ 1071 1074 IBD IBD NNP 1075 1083 patients patient NNS 1084 1088 were be VBD 1089 1102 significantly significantly RB 1103 1108 lower low JJR 1109 1113 than than IN 1114 1119 those those DT 1120 1122 of of IN 1123 1130 control control JJ 1131 1139 subjects subject NNS 1140 1141 ( ( ( 1141 1145 59.6 59.6 CD 1146 1149 +/- +/- SYM 1150 1154 57.1 57.1 CD 1155 1158 dpm dpm NN 1159 1163 mg-1 mg-1 NN 1164 1171 cytosol cytosol NN 1172 1179 protein protein NN 1180 1183 vs. vs. IN 1184 1189 227.0 227.0 CD 1190 1193 +/- +/- SYM 1194 1198 90.8 90.8 CD 1199 1202 dpm dpm NN 1203 1207 mg-1 mg-1 NN 1208 1215 cytosol cytosol NN 1216 1223 protein protein NN 1223 1224 , , , 1225 1226 P p NN 1227 1228 = = SYM 1229 1234 0.007 0.007 CD 1234 1235 ) ) ) 1236 1239 and and CC 1240 1243 IBD IBD NNP 1244 1252 patients patient NNS 1253 1256 not not RB 1257 1266 receiving receive VBG 1267 1281 glucocorticoid glucocorticoid NN 1282 1291 treatment treatment NN 1292 1293 ( ( ( 1293 1298 179.7 179.7 CD 1299 1302 +/- +/- SYM 1303 1308 171.3 171.3 CD 1309 1312 dpm dpm NN 1313 1317 mg-1 mg-1 NN 1318 1325 cytosol cytosol NN 1326 1333 protein protein NN 1333 1334 , , , 1335 1336 P p NN 1337 1338 = = SYM 1339 1344 0.002 0.002 CD 1344 1345 ) ) ) 1345 1346 . . . 1347 1355 Systemic systemic JJ 1356 1359 hGR hGR NNP 1360 1366 levels level NNS 1367 1369 in in IN 1370 1379 untreated untreated JJ 1380 1383 IBD IBD NNP 1384 1392 patients patient NNS 1393 1396 did do VBD 1397 1400 not not RB 1401 1407 differ differ VB 1408 1421 significantly significantly RB 1422 1426 from from IN 1427 1432 those those DT 1433 1435 in in IN 1436 1443 control control JJ 1444 1452 subjects subject NNS 1452 1453 . . . 1454 1456 In in IN 1457 1465 patients patient NNS 1466 1470 with with IN 1471 1481 connective connective JJ 1482 1488 tissue tissue NN 1489 1497 diseases disease NNS 1497 1498 , , , 1499 1507 systemic systemic JJ 1508 1511 hGR hGR NNP 1512 1518 levels level NNS 1519 1523 were be VBD 1524 1528 also also RB 1529 1534 found find VBN 1535 1537 to to TO 1538 1540 be be VB 1541 1550 decreased decrease VBN 1551 1553 in in IN 1554 1557 the the DT 1558 1565 absence absence NN 1566 1568 of of IN 1569 1583 glucocorticoid glucocorticoid NN 1584 1593 treatment treatment NN 1593 1594 . . . 1595 1603 Systemic systemic JJ 1604 1607 hGR hGR NNP 1608 1614 levels level NNS 1615 1617 in in IN 1618 1626 patients patient NNS 1627 1631 with with IN 1632 1637 Crohn Crohn NNP 1637 1639 ’s 's POS 1640 1647 disease disease NN 1648 1649 ( ( ( 1649 1651 CD cd NN 1651 1652 ) ) ) 1653 1660 treated treat VBN 1661 1665 with with IN 1666 1674 steroids steroid NNS 1675 1676 ( ( ( 1676 1680 66.6 66.6 CD 1681 1684 +/- +/- SYM 1685 1689 61.0 61.0 CD 1690 1693 dpm dpm NN 1694 1698 mg-1 mg-1 NN 1699 1706 cytosol cytosol NN 1707 1714 protein protein NN 1714 1715 ) ) ) 1716 1720 were be VBD 1721 1724 not not RB 1725 1734 different different JJ 1735 1739 from from IN 1740 1745 those those DT 1746 1748 in in IN 1749 1757 patients patient NNS 1758 1762 with with IN 1763 1773 ulcerative ulcerative JJ 1774 1781 colitis colitis NN 1782 1783 ( ( ( 1783 1785 UC UC NNP 1785 1786 ) ) ) 1787 1788 ( ( ( 1788 1792 56.1 56.1 CD 1793 1796 +/- +/- SYM 1797 1801 51.6 51.6 CD 1802 1805 dpm dpm NN 1806 1810 mg-1 mg-1 NN 1811 1818 cytosol cytosol NN 1819 1826 protein protein NN 1826 1827 ) ) ) 1827 1828 . . . 1829 1831 In in IN 1832 1840 contrast contrast NN 1841 1843 to to TO 1844 1849 these these DT 1850 1858 findings finding NNS 1858 1859 , , , 1860 1867 mucosal mucosal JJ 1868 1871 hGR hGR NNP 1872 1878 levels level NNS 1879 1883 were be VBD 1884 1897 significantly significantly RB 1898 1907 decreased decrease VBN 1908 1910 in in IN 1911 1915 both both CC 1916 1931 steroid-treated steroid-treated JJ 1932 1933 ( ( ( 1933 1937 18.0 18.0 CD 1938 1941 +/- +/- CC 1942 1946 15.5 15.5 CD 1946 1947 ) ) ) 1948 1951 and and CC 1952 1955 not not RB 1956 1971 steroid-treated steroid-treated JJ 1972 1973 ( ( ( 1973 1977 37.8 37.8 CD 1978 1981 +/- +/- CC 1982 1986 30.5 30.5 CD 1986 1987 ) ) ) 1988 1996 patients patient NNS 1997 2005 compared compare VBN 2006 2010 with with IN 2011 2018 control control JJ 2019 2027 subjects subject NNS 2028 2029 ( ( ( 2030 2035 125.6 125.6 CD 2036 2039 +/- +/- CC 2040 2044 97.1 97.1 CD 2044 2045 ; ; : 2046 2047 P p NN 2048 2049 = = SYM 2050 2057 0.00009 0.00009 CD 2058 2061 and and CC 2062 2063 P p NN 2064 2065 = = SYM 2066 2072 0.0008 0.0008 CD 2073 2085 respectively respectively RB 2086 2087 ) ) ) 2087 2088 . . . 2089 2093 IL-6 il-6 NN 2094 2100 levels level NNS 2101 2103 in in IN 2104 2107 all all DT 2108 2111 IBD ibd NN 2112 2118 groups group NNS 2119 2123 with with IN 2124 2127 and and CC 2128 2135 without without IN 2136 2144 steroids steroid NNS 2145 2149 were be VBD 2150 2163 significantly significantly RB 2164 2173 different different JJ 2174 2178 from from IN 2179 2184 those those DT 2185 2187 in in IN 2188 2195 control control JJ 2196 2204 subjects subject NNS 2204 2205 . . . 2206 2216 CONCLUSION conclusion NN 2216 2217 : : : 2218 2220 In in IN 2221 2224 IBD IBD NNP 2225 2230 there there EX 2231 2233 is be VBZ 2234 2236 no no DT 2237 2247 difference difference NN 2248 2250 in in IN 2251 2259 systemic systemic JJ 2260 2263 hGR hGR NNP 2264 2270 levels level NNS 2271 2278 between between IN 2279 2282 not not RB 2283 2298 steroid-treated steroid-treated JJ 2299 2307 patients patient NNS 2308 2311 and and CC 2312 2319 control control JJ 2320 2328 subjects subject NNS 2328 2329 , , , 2330 2332 in in IN 2333 2338 spite spite NN 2339 2341 of of IN 2342 2354 inflammatory inflammatory JJ 2355 2363 activity activity NN 2364 2365 ( ( ( 2365 2369 IL-6 IL-6 NNP 2369 2370 ) ) ) 2370 2371 . . . 2372 2379 Mucosal mucosal JJ 2380 2383 hGR hGR NNP 2384 2390 levels level NNS 2391 2395 were be VBD 2396 2405 decreased decrease VBN 2406 2419 independently independently RB 2420 2422 of of IN 2423 2432 treatment treatment NN 2432 2433 , , , 2434 2442 probably probably RB 2443 2450 leading lead VBG 2451 2453 to to TO 2454 2455 a a DT 2456 2465 decreased decrease VBN 2466 2476 protection protection NN 2477 2484 against against IN 2485 2494 NF-kappaB NF-kappaB NNP 2495 2501 action action NN 2502 2504 in in IN 2505 2508 the the DT 2509 2519 intestinal intestinal JJ 2520 2526 mucosa mucosa NN 2526 2527 . . .