0 4 Some some DT 5 17 antioxidants antioxidant NNS 18 25 inhibit inhibit VBP 25 26 , , , 27 29 in in IN 30 31 a a DT 32 43 co-ordinate co-ordinate JJ 44 51 fashion fashion NN 51 52 , , , 53 56 the the DT 57 67 production production NN 68 70 of of IN 71 76 tumor tumor NN 77 85 necrosis necrosis NN 86 98 factor-alpha factor-alpha NN 98 99 , , , 100 107 IL-beta IL-beta NNP 107 108 , , , 109 112 and and CC 113 117 IL-6 il-6 NN 118 120 by by IN 121 126 human human JJ 127 137 peripheral peripheral JJ 138 143 blood blood NN 144 155 mononuclear mononuclear JJ 156 161 cells cell NNS 161 162 . . . 164 168 Some some DT 169 181 antioxidants antioxidant NNS 181 182 , , , 183 192 including include VBG 193 202 butylated butylate VBN 203 217 hydroxyanisole hydroxyanisole NN 218 219 ( ( ( 219 222 BHA BHA NNP 222 223 ) ) ) 223 224 , , , 225 247 tetrahydropapaveroline tetrahydropapaveroline NN 248 249 ( ( ( 249 252 THP THP NNP 252 253 ) ) ) 253 254 , , , 255 275 nordihydroguiauretic nordihydroguiauretic JJ 276 280 acid acid NN 280 281 , , , 282 285 and and CC 286 310 10,11-dihydroxyaporphine 10,11-dihydroxyaporphine NN 311 312 ( ( ( 312 315 DHA DHA NNP 315 316 ) ) ) 316 317 , , , 318 322 were be VBD 323 328 found find VBN 329 331 to to TO 332 334 be be VB 335 341 potent potent JJ 342 352 inhibitors inhibitor NNS 353 355 of of IN 356 359 the the DT 360 370 production production NN 371 373 of of IN 374 379 tumor tumor NN 380 388 necrosis necrosis NN 389 395 factor factor NN 396 397 ( ( ( 397 407 TNF)-alpha TNF)-alpha NNP 407 408 , , , 409 413 IL-1 il-1 NN 414 418 beta beta NN 418 419 , , , 420 423 and and CC 424 428 IL-6 il-6 NN 429 431 by by IN 432 437 human human JJ 438 448 peripheral peripheral JJ 449 454 blood blood NN 455 466 mononuclear mononuclear JJ 467 472 cells cell NNS 473 474 ( ( ( 474 478 PBMC PBMC NNP 478 479 ) ) ) 480 490 stimulated stimulate VBN 491 493 by by IN 494 512 lipopolysaccharide lipopolysaccharide NN 513 514 ( ( ( 514 517 LPS LPS NNP 517 518 ) ) ) 519 520 ( ( ( 520 525 IC50s IC50 NNP 526 528 in in IN 529 532 the the DT 533 536 low low JJ 537 547 micromolar micromolar JJ 548 553 range range NN 553 554 ) ) ) 554 555 . . . 556 566 Inhibition Inhibition NNP 567 569 of of IN 570 578 cytokine cytokine NN 579 589 production production NN 590 593 was be VBD 594 598 gene gene NN 599 608 selective selective JJ 609 612 and and CC 613 616 not not RB 617 620 due due JJ 621 623 to to TO 624 631 general general JJ 632 639 effects effect NNS 640 642 on on IN 643 650 protein protein NN 651 660 synthesis synthesis NN 660 661 . . . 662 672 Inhibition Inhibition NNP 673 675 of of IN 676 684 cytokine cytokine NN 685 695 production production NN 696 698 by by IN 699 703 PBMC PBMC NNP 704 707 was be VBD 708 716 observed observe VBN 717 721 also also RB 722 726 when when WRB 727 732 other other JJ 733 741 inducers inducer NNS 742 746 were be VBD 747 751 used use VBN 752 753 ( ( ( 753 766 staphylococci staphylococci NNS 766 767 , , , 768 774 silica silica NN 774 775 , , , 776 783 zymosan zymosan NN 783 784 ) ) ) 784 785 . . . 786 790 Much much RB 791 797 higher high JJR 798 812 concentrations concentration NNS 813 815 of of IN 816 821 other other JJ 822 845 antioxidants–including antioxidants–include VBG 846 854 ascorbic ascorbic JJ 855 859 acid acid NN 859 860 , , , 861 867 trolox trolox NN 867 868 , , , 869 885 alpha-tocopherol alpha-tocopherol NN 885 886 , , , 887 896 butylated butylate VBN 897 911 hydroxytoluene hydroxytoluene NN 911 912 , , , 913 916 and and CC 917 920 the the DT 921 935 5-lipoxygenase 5-lipoxygenase NN 936 945 inhibitor inhibitor NN 946 959 zileuton–did zileuton–did VBD 960 963 not not RB 964 970 affect affect VB 971 974 the the DT 975 985 production production NN 986 988 of of IN 989 994 these these DT 995 1004 cytokines cytokine NNS 1004 1005 . . . 1006 1009 The the DT 1010 1016 active active JJ 1017 1026 compounds compound NNS 1027 1030 did do VBD 1031 1034 not not RB 1035 1042 inhibit inhibit VB 1043 1055 IL-1-induced il-1-induced JJ 1056 1066 production production NN 1067 1069 of of IN 1070 1074 IL-6 il-6 NN 1075 1077 in in IN 1078 1089 fibroblasts fibroblast NNS 1089 1090 , , , 1091 1098 showing show VBG 1099 1102 the the DT 1103 1107 cell cell NN 1108 1119 selectivity selectivity NN 1120 1122 of of IN 1123 1126 the the DT 1127 1133 effect effect NN 1133 1134 . . . 1135 1155 Antioxidant-mediated antioxidant-mediated JJ 1156 1166 inhibition inhibition NN 1167 1169 of of IN 1170 1178 cytokine cytokine NN 1179 1189 production production NN 1190 1193 was be VBD 1194 1204 correlated correlate VBN 1205 1209 with with IN 1210 1213 low low JJ 1214 1220 levels level NNS 1221 1223 of of IN 1224 1227 the the DT 1228 1241 corresponding correspond VBG 1242 1251 messenger messenger NN 1252 1256 RNAs rna NNS 1256 1257 . . . 1258 1265 Nuclear nuclear JJ 1266 1272 run-on run-on JJ 1273 1284 experiments experiment NNS 1285 1291 showed show VBD 1292 1296 that that IN 1297 1300 THP THP NNP 1301 1310 inhibited inhibit VBD 1311 1324 transcription transcription NN 1325 1327 of of IN 1328 1331 the the DT 1332 1336 IL-1 il-1 NN 1337 1341 beta beta NN 1342 1346 gene gene NN 1346 1347 . . . 1348 1351 THP THP NNP 1352 1361 decreased decrease VBD 1362 1365 the the DT 1366 1379 concentration concentration NN 1380 1382 of of IN 1383 1386 the the DT 1387 1400 transcription transcription NN 1401 1408 factors factor NNS 1409 1417 NF-kappa NF-kappa NNP 1418 1419 B B NNP 1420 1423 and and CC 1424 1428 AP-1 AP-1 NNP 1429 1437 detected detect VBN 1438 1440 in in IN 1441 1448 nuclear nuclear JJ 1449 1457 extracts extract NNS 1458 1460 of of IN 1461 1465 PBMC PBMC NNP 1466 1474 cultured culture VBN 1475 1477 in in IN 1478 1481 the the DT 1482 1490 presence presence NN 1491 1493 or or CC 1494 1501 absence absence NN 1502 1504 of of IN 1505 1508 LPS LPS NNP 1508 1509 . . . 1510 1513 THP THP NNP 1514 1517 and and CC 1518 1521 DHA DHA NNP 1522 1530 markedly markedly RB 1531 1540 decreased decrease VBD 1541 1544 the the DT 1545 1551 levels level NNS 1552 1554 of of IN 1555 1564 TNF-alpha TNF-alpha NNP 1565 1568 and and CC 1569 1573 IL-1 il-1 NN 1574 1578 beta beta NN 1579 1581 in in IN 1582 1585 the the DT 1586 1597 circulation circulation NN 1598 1600 of of IN 1601 1605 mice mouse NNS 1606 1615 following follow VBG 1616 1619 LPS LPS NNP 1620 1629 injection injection NN 1629 1630 . . . 1631 1635 Thus thus RB 1636 1648 antioxidants antioxidant NNS 1649 1653 vary vary VBP 1654 1660 widely widely RB 1661 1663 in in IN 1664 1671 potency potency NN 1672 1674 as as IN 1675 1685 inhibitors inhibitor NNS 1686 1688 of of IN 1689 1692 the the DT 1693 1703 activation activation NN 1704 1706 of of IN 1707 1720 transcription transcription NN 1721 1728 factors factor NNS 1729 1732 and and CC 1733 1735 of of IN 1736 1739 the the DT 1740 1753 transcription transcription NN 1754 1756 of of IN 1757 1762 genes gene NNS 1763 1766 for for IN 1767 1783 pro-inflammatory pro-inflammatory JJ 1784 1793 cytokines cytokine NNS 1793 1794 . . . 1795 1805 Coordinate coordinate JJ 1806 1816 inhibition inhibition NN 1817 1819 of of IN 1820 1823 the the DT 1824 1837 transcription transcription NN 1838 1840 of of IN 1841 1846 genes gene NNS 1847 1850 for for IN 1851 1863 inflammatory inflammatory JJ 1864 1873 cytokines cytokine NNS 1874 1879 could could MD 1880 1887 provide provide VB 1888 1889 a a DT 1890 1898 strategy strategy NN 1899 1902 for for IN 1903 1910 therapy therapy NN 1911 1913 of of IN 1914 1922 diseases disease NNS 1923 1927 with with IN 1928 1940 inflammatory inflammatory JJ 1941 1953 pathogenesis pathogenesis NN 1954 1957 and and CC 1958 1961 for for IN 1962 1968 septic septic JJ 1969 1974 shock shock NN 1974 1975 . . .