0 9 Tyloxapol Tyloxapol NNP 10 18 inhibits inhibit VBZ 19 27 NF-kappa NF-kappa NNP 28 29 B B NNP 30 33 and and CC 34 42 cytokine cytokine NN 43 50 release release NN 50 51 , , , 52 61 scavenges scavenge VBZ 62 66 HOCI HOCI NNP 66 67 , , , 68 71 and and CC 72 79 reduces reduce VBZ 80 89 viscosity viscosity NN 90 92 of of IN 93 99 cystic cystic JJ 100 108 fibrosis fibrosis NN 109 115 sputum sputum NN 115 116 . . . 118 124 Cystic cystic JJ 125 133 fibrosis fibrosis NN 134 135 ( ( ( 135 137 CF CF NNP 137 138 ) ) ) 139 147 patients patient NNS 148 155 develop develop VBP 156 167 progressive progressive JJ 168 185 cytokine-mediated cytokine-mediated JJ 186 198 inflammatory inflammatory JJ 199 203 lung lung NN 204 211 disease disease NN 211 212 , , , 213 217 with with IN 218 226 abundant abundant JJ 227 237 production production NN 238 240 of of IN 241 246 thick thick JJ 246 247 , , , 248 257 tenacious tenacious JJ 257 258 , , , 259 268 protease- protease- NN 269 272 and and CC 273 285 oxidant-rich oxidant-rich JJ 286 294 purulent purulent JJ 295 301 airway airway NN 302 312 secretions secretion NNS 313 317 that that WDT 318 321 are be VBP 322 331 difficult difficult JJ 332 334 to to TO 335 340 clear clear VB 341 345 even even RB 346 350 with with IN 351 364 physiotherapy physiotherapy NN 364 365 . . . 366 368 In in IN 369 372 the the DT 373 379 search search NN 380 383 for for IN 384 385 a a DT 386 395 potential potential JJ 396 405 treatment treatment NN 405 406 , , , 407 409 we we PRP 410 414 have have VBP 415 421 tested test VBN 422 431 tyloxapol tyloxapol NN 431 432 , , , 433 435 an an DT 436 445 alkylaryl alkylaryl NN 446 455 polyether polyether NN 456 463 alcohol alcohol NN 464 471 polymer polymer NN 472 481 detergent detergent NN 482 492 previously previously RB 493 497 used use VBN 498 500 as as IN 501 502 a a DT 503 512 mucolytic mucolytic JJ 513 518 agent agent NN 519 521 in in IN 522 527 adult adult JJ 528 535 chronic chronic JJ 536 546 bronchitis bronchitis NN 546 547 . . . 548 557 Tyloxapol Tyloxapol NNP 558 566 inhibits inhibit VBZ 567 577 activation activation NN 578 580 of of IN 581 584 the the DT 585 598 transcription transcription NN 599 605 factor factor NN 606 613 nuclear nuclear JJ 614 626 factor-kappa factor-kappa NN 627 628 B B NNP 629 630 ( ( ( 630 638 NK-kappa NK-kappa NNP 639 640 B B NNP 640 641 ) ) ) 641 642 , , , 643 650 reduces reduce VBZ 651 658 resting rest VBG 659 668 secretion secretion NN 669 671 of of IN 672 675 the the DT 676 684 cytokine cytokine NN 685 698 interleukin-8 interleukin-8 NN 699 700 ( ( ( 700 704 IL-8 il-8 NN 704 705 ) ) ) 706 708 in in IN 709 717 cultured culture VBN 718 723 human human JJ 724 733 monocytes monocyte NNS 733 734 , , , 735 738 and and CC 739 747 inhibits inhibit VBZ 748 766 lipopolysaccharide lipopolysaccharide NN 767 768 ( ( ( 768 783 LPS)-stimulated lps)-stimulated JJ 784 791 release release NN 792 794 of of IN 795 800 tumor tumor NN 801 809 necrosis necrosis NN 810 822 factor-alpha factor-alpha NN 823 824 ( ( ( 824 833 TNF-alpha TNF-alpha NNP 833 834 ) ) ) 834 835 , , , 836 840 IL-1 il-1 NN 841 845 beta beta NN 845 846 , , , 847 851 IL-6 IL-6 NNP 851 852 , , , 853 857 IL-8 IL-8 NNP 857 858 , , , 859 881 granulocyte-macrophage granulocyte-macrophage JJ 882 900 colony-stimulating colony-stimulating JJ 901 907 factor factor NN 908 909 ( ( ( 909 915 GM-CSF GM-CSF NNP 915 916 ) ) ) 916 917 , , , 918 921 and and CC 922 925 the the DT 926 938 eiconsanoids eiconsanoid NNS 939 950 thromboxane thromboxane NN 951 953 A2 a2 NN 954 957 and and CC 958 969 leukotriene leukotriene NN 970 972 B4 b4 NN 973 974 ( ( ( 974 978 LTB4 ltb4 NN 978 979 ) ) ) 979 980 . . . 981 983 We we PRP 984 988 have have VBP 989 999 previously previously RB 1000 1005 shown show VBN 1006 1010 that that IN 1011 1020 tyloxapol tyloxapol NN 1021 1023 is be VBZ 1024 1025 a a DT 1026 1032 potent potent JJ 1033 1044 antioxidant antioxidant NN 1045 1048 for for IN 1049 1057 hydroxyl hydroxyl NN 1058 1066 radicals radical NNS 1067 1068 ( ( ( 1069 1073 OH). OH). NNP 1074 1083 Tyloxapol Tyloxapol NNP 1084 1085 ( ( ( 1085 1089 0.05 0.05 CD 1090 1092 to to TO 1093 1096 0.1 0.1 CD 1096 1097 % % NN 1098 1104 wt/vol wt/vol NN 1104 1105 ) ) ) 1106 1117 effectively effectively RB 1118 1127 scavenges scavenge VBZ 1128 1131 the the DT 1132 1139 oxidant oxidant JJ 1140 1152 hypochlorous hypochlorous JJ 1153 1157 acid acid NN 1158 1159 ( ( ( 1159 1163 HOCl HOCl NNP 1163 1164 ; ; : 1165 1166 1 1 CD 1167 1169 to to TO 1170 1173 7.5 7.5 CD 1174 1176 mM mm NN 1176 1177 ) ) ) 1178 1180 in in FW 1181 1186 vitro vitro FW 1186 1187 , , , 1188 1191 and and CC 1192 1200 protects protect VBZ 1201 1205 from from IN 1206 1219 HOCl-mediated hocl-mediated JJ 1220 1224 lung lung NN 1225 1231 injury injury NN 1232 1234 in in IN 1235 1239 rats rat NNS 1239 1240 . . . 1241 1250 Tyloxapol Tyloxapol NNP 1251 1255 also also RB 1256 1263 reduces reduce VBZ 1264 1267 the the DT 1268 1277 viscosity viscosity NN 1278 1280 of of IN 1281 1283 CF CF NNP 1284 1290 sputum sputum NN 1291 1292 ( ( ( 1292 1296 from from IN 1297 1300 463 463 CD 1301 1304 +/- +/- SYM 1305 1308 133 133 CD 1309 1311 to to TO 1312 1315 128 128 CD 1316 1319 +/- +/- SYM 1320 1322 52 52 CD 1323 1333 centipoise centipoise NN 1333 1334 ) ) ) 1334 1335 . . . 1336 1338 We we PRP 1339 1347 conclude conclude VBP 1348 1352 that that IN 1353 1362 tyloxapol tyloxapol NN 1363 1365 is be VBZ 1366 1377 potentially potentially RB 1378 1384 useful useful JJ 1385 1387 as as IN 1388 1389 a a DT 1390 1393 new new JJ 1394 1410 antiinflammatory antiinflammatory JJ 1411 1418 therapy therapy NN 1419 1422 for for IN 1423 1425 CF CF NNP 1426 1430 lung lung NN 1431 1438 disease disease NN 1438 1439 , , , 1440 1443 and and CC 1444 1449 could could MD 1450 1458 possibly possibly RB 1459 1466 promote promote VB 1467 1476 clearance clearance NN 1477 1479 of of IN 1480 1490 secretions secretion NNS 1491 1493 in in IN 1494 1497 the the DT 1498 1500 CF CF NNP 1501 1507 airway airway NN 1507 1508 . . .