Tetrabromobisphenol A and hexabromocyclododecane alter secretion of IL-1β from human immune cells

Figures & data

Figure 1. Effects of exposures to TBBPA on IL-1β secretion from human NK cells, monocyte-depleted PBMC and PBMC. (a) NK cells (donor KB129). (b) Monocyte-depleted PBMC (donor F177). (c) PBMC (donor F188). All doses 0.05–5.0 μM TBBPA. Data shown are means ± SD. * Value significantly different from appropriate control (0 μM) at p < 0.05.

Table 1. Effects of TBBPA exposures on IL-1β secretion from highly purified human NK cells.

[TBBPA] μM	KB129	KB130	KB181	KB183	KB184
24 h
0	284 ± 34	191 ± 6	220 ± 116	2942 ± 69	1355 ± 26
0.05	1942 ± 37*	630 ± 25*	1172 ± 127*	2358 ± 41*	995 ± 66*
0.1	1889 ± 239*	521 ± 47*	1180 ± 152*	2284 ± 67*	898 ± 55*
0.25	611 ± 3*	411 ± 38*	879 ± 141*	2465 ± 49*	861 ± 9*
0.5	828 ± 55*	185 ± 38	744 ± 115*	1826 ± 61*	822 ± 37*
1	554 ± 27*	63 ± 30*	429 ± 98	1055 ± 94*	1110 ± 23*
2.5	274 ± 84	56 ± 22*	139 ± 49	820 ± 43*	1025 ± 36*
5	0 ± 55*	0 ± 19*	142 ± 104	459 ± 40*	428 ± 19*
48 h
0	112 ± 20	332 ± 104	877 ± 56	1974 ± 109	1080 ± 29
0.05	295 ± 52*	222 ± 28	3005 ± 101*	3475 ± 40*	1448 ± 50*
0.1	233 ± 38*	564 ± 56*	2279 ± 14*	3051 ± 36*	1645 ± 45*
0.25	222 ± 31*	159 ± 88	2603 ± 254*	2555 ± 40*	1397 ± 75*
0.5	253 ± 29*	186 ± 93	3388 ± 104*	2469 ± 32*	1123 ± 53
1	168 ± 30	83 ± 1	2338 ± 97*	1810 ± 10	1187 ± 61
2.5	89 ± 14	292 ± 101	799 ± 49	1612 ± 69*	1072 ± 95
5	0 ± 5*	0 ± 46*	924 ± 103	1436 ± 55*	453 ± 16*
6 days
0	476 ± 41	90 ± 40	193 ± 33	164 ± 9	1368 ± 106
0.05	1401 ± 152*	452 ± 22*	1438 ± 26*	1585 ± 33*	1360 ± 85
0.1	833 ± 119*	465 ± 21*	1737 ± 143*	1770 ± 58*	1170 ± 20
0.25	548 ± 24*	476 ± 49*	1204 ± 40*	1580 ± 13*	1189 ± 59
0.5	726 ± 126	379 ± 32*	1041 ± 84*	802 ± 53*	1119 ± 11
1	413 ± 7	411 ± 22*	691 ± 49*	762 ± 83*	1193 ± 24
2.5	421 ± 42	303 ± 19*	328 ± 61*	632 ± 77*	1226 ± 9
5	202 ± 12*	74 ± 33	296 ± 16	242 ± 18*	563 ± 14*

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates a significant change in secretion compared to control cells (cells treated with vehicle alone), p < 0.05.

Table 2. Effects of TBBPA exposures to on IL -1β secretion from monocyte-depleted PBMC.

[TBBPA] μM	F 175	F 177	F 180	F 184
24 h
0	1751 ± 31	1103 ± 43	4465 ± 8	714 ± 103
0.05	1417 ± 142*	2393 ± 457*	4807 ± 139*	6869 ± 345*
0.1	1198 ± 23*	1898 ± 446	4088 ± 79*	5478 ± 856*
0.25	1527 ± 106	1098 ± 19-	2777 ± 33*	1743 ± 233*
0.5	1409 ± 73*	608 ± 219	2268 ± 178*	1294 ± 36*
1	778 ± 30*	670 ± 58*	1645 ± 157*	1311 ± 635*
2.5	790 ± 71*	308 ± 41*	957 ± 129*	938 ± 34
5	578 ± 18*	179 ± 50*	1544 ± 80*	737 ± 125
48 h
0	3086 ± 173	2381 ± 189	5539 ± 216	618 ± 35
0.05	3061 ± 338	2178 ± 124	4826 ± 229*	765 ± 166
0.1	2691 ± 354	1918 ± 48*	4212 ± 129*	595 ± 115
0.25	1850 ± 140*	2220 ± 263	2726 ± 167*	720 ± 93
0.5	3045 ± 116	1918 ± 24*	2563 ± 79*	573 ± 94
1	3014 ± 102	1480 ± 1128	2720 ± 239*	601 ± 10
2.5	1594 ± 77*	1371 ± 48*	2475 ± 56*	1415 ± 93*
5	1178 ± 31*	1272 ± 15*	4680 ± 117*	2347 ± 81*
6 days
0	1458 ± 15	3054 ± 253	2960 ± 128	371 ± 26
0.05	4149 ± 113*	13 725 ± 175*	2938 ± 108	2975 ± 450*
0.1	3238 ± 42*	3025 ± 78	2321 ± 168*	1894 ± 336*
0.25	2918 ± 192*	5479 ± 189*	1857 ± 234*	1998 ± 263*
0.5	2468 ± 137*	4000 ± 113*	780 ± 55*	1360 ± 156*
1	1417 ± 22	2167 ± 69*	1285 ± 110*	1429 ± 88*
2.5	3426 ± 82*	2646 ± 182	1915 ± 135*	1348 ± 302*
5	559 ± 21*	1946 ± 71*	1951 ± 41*	1544 ± 81*

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates a significant change in secretion compared to control cells (cells treated with vehicle alone), p < 0.05.

Table 3. Effects of TBBPA exposures to TBBPA on IL-1β secretion from PBMC.

[TBBPA] μM	F 186	F 187	F 188	F 193	F 194
24 h
0	4834 ± 103	3057 ± 235	3240 ± 72	3648 ± 73	1585 ± 185
0.05	5530 ± 73*	3425 ± 153	3020 ± 413	3186 ± 167*	3872 ± 322*
0.1	5608 ± 132*	2582 ± 184	2299 ± 10*	3091 ± 108*	3526 ± 56*
0.25	3530 ± 103*	2405 ± 175*	1942 ± 32*	3098 ± 62*	2986 ± 125*
0.5	3065 ± 148*	2400 ± 298*	2020 ± 17*	2801 ± 44*	2440 ± 203*
1	1620 ± 23*	2137 ± 206*	1209 ± 77*	2772 ± 39*	1128 ± 105*
2.5	3407 ± 13*	5430 ± 224*	844 ± 203*	2630 ± 93*	913 ± 13*
5	1073 ± 43*	3142 ± 15	1479 ± 41*	1616 ± 28*	753 ± 113*
48 h
0	3985 ± 54	2649 ± 88	2620 ± 98	6758 ± 258	3788 ± 170
0.05	4370 ± 207	2557 ± 156	2639 ± 165	6309 ± 199	3059 ± 187*
0.1	3447 ± 141*	15 548 ± 186*	3330 ± 292*	6147 ± 80*	2776 ± 176*
0.25	2194 ± 109*	1552 ± 121*	2330 ± 128*	6665 ± 197	2934 ± 478
0.5	3013 ± 328*	1672 ± 46*	2159 ± 89*	6542 ± 232	3070 ± 202*
1	4161 ± 266	1661 ± 36*	2178 ± 125*	6227 ± 116	2692 ± 78*
2.5	9101 ± 481*	4195 ± 164*	2232 ± 228	6941 ± 164	2980 ± 195*
5	3756 ± 319	7046 ± 140*	3007 ± 59*	4456 ± 460*	2533 ± 157*
6 days
0	3661 ± 180	1580 ± 158	1845 ± 28	12 484 ± 398	805 ± 56
0.05	3634 ± 404	1808 ± 79	1808 ± 106	8655 ± 238*	1199 ± 64*
0.1	3625 ± 140	1147 ± 76*	1845 ± 38	9868 ± 923*	1022 ± 100*
0.25	3278 ± 305	1019 ± 157*	1881 ± 84	9817 ± 792*	898 ± 63
0.5	995 ± 117*	750 ± 79*	1918 ± 73	9791 ± 671*	882 ± 116
1	2517 ± 108*	732 ± 127*	1796 ± 96	9509 ± 260*	608 ± 24*
2.5	3337 ± 264	2253 ± 265*	1875 ± 103	11 802 ± 645	520 ± 87*
5	5995 ± 196*	12 007 ± 690*	2002 ± 42*	5166 ± 169*	592 ± 186

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates a significant change in secretion compared to control cells (cells treated with vehicle alone), p < 0.05.

Table 4. Effects of HBCD exposures to on IL -1β secretion from highly-purified human NK cells.

[HBCD] μM	KB179	KB181	KB182
24 h
0	295 ± 7	275 ± 19	933 ± 33
0.05	279 ± 8	829 ± 31*	1385 ± 63*
0.1	348 ± 10*	620 ± 54*	1536 ± 67*
0.25	353 ± 10*	827 ± 28*	1446 ± 39*
0.5	389 ± 8*	623 ± 52*	1752 ± 63*
1	416 ± 13*	860 ± 98*	2006 ± 26*
2.5	426 ± 17*	6356 ± 76*	1911 ± 34*
5	213 ± 21*	5914 ± 76*	1358 ± 70*
48 h
0	222 ± 13	959 ± 20	984 ± 86
0.05	360 ± 7*	1728 ± 77*	2673 ± 10*
0.1	364 ± 15*	2231 ± 59*	2403 ± 49*
0.25	428 ± 1*	1854 ± 60*	3158 ± 72*
0.5	420 ± 16*	2111 ± 95*	2870 ± 109*
1	475 ± 11*	4139 ± 56*	3100 ± 116*
2.5	449 ± 18*	10 087 ± 397*	3420 ± 150*
5	112 ± 1*	8731 ± 169*	1045 ± 73*
6 days
0	245 ± 45	2509 ± 128	972 ± 45*
0.05	610 ± 46*	2415 ± 71	2465 ± 75*
0.1	646 ± 27*	3106 ± 134*	2003 ± 32*
0.25	443 ± 83*	2932 ± 84*	2058 ± 115*
0.5	423 ± 34*	3119 ± 116*	1833 ± 102*
1	385 ± 66*	4534 ± 157*	2007 ± 18*
2.5	245 ± 45	6614 ± 405*	1317 ± 76*
5	156 ± 3	7542 ± 169*	1186 ± 38*

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates a significant change in secretion compared to control cells (cells treated with vehicle alone), p < 0.05.

Figure 2. Effects of exposures to HBCD on IL-1β secretion from human NK cells, monocyte-depleted PBMC and PBMC. (a) NK cells (donor KB181). (b) Monocyte-depleted PBMC (donor F202). (c) PBMC (donor F189). All doses 0.05–5.0 μM HBCD. Data shown are means ± SD. * Value significantly different from appropriate control at p < 0.05.

Table 5. Effects of HBCD exposures on IL -1β secretion from monocyte-depleted PBMC.

[HBCD] μM	F 196	F 198	F 202	F 204	F 212
24 h
0	13 357 ± 405	472 ± 99	1159 ± 534	3248 ± 156	140 ± 6
0.05	10 959 ± 136*	2159 ± 247*	2439 ± 308*	3969 ± 146*	3169 ± 134*
0.1	13 819 ± 434	1344 ± 159*	1568 ± 279	2825 ± 31*	3231 ± 168*
0.25	11 888 ± 181*	1316 ± 267*	1815 ± 210	4327 ± 86*	3264 ± 111*
0.5	16 171 ± 389*	820 ± 159*	3095 ± 703*	3914 ± 279*	3730 ± 166*
1	15 914 ± 328*	2358 ± 84*	9492 ± 1378*	6735 ± 105*	2004 ± 283*
2.5	22 644 ± 1785*	22 427 ± 539*	38 224 ± 568*	23 059 ± 1288*	12 008 ± 448*
5	27 027 ± 2079*	26 757 ± 1975*	47 052 ± 5925*	33 407 ± 291*	18 484 ± 279*
48 h
0	10 065 ± 167	732 ± 241	2869 ± 597	2527 ± 88	51 ± 32
0.05	18 636 ± 372*	742 ± 285	2791 ± 444	3927 ± 379*	1421 ± 533*
0.1	17 737 ± 344*	56 ± 44*	2180 ± 219	3556 ± 329*	480 ± 21*
0.25	16 910 ± 249*	993 ± 193	4024 ± 310	3556 ± 183*	1458 ± 147*
0.5	14 375 ± 522*	182 ± 44	5013 ± 296*	3725 ± 300*	2259 ± 38*
1	12 735 ± 600*	2356 ± 243*	8458 ± 403*	10 214 ± 89*	1715 ± 59*
2.5	15 908 ± 1214*	31 196 ± 5128*	28 980 ± 2137*	53 843 ± 1168*	14 834 ± 566*
5	13 784 ± 844*	44 452 ± 2611*	47 813 ± 3328*	45 151 ± 3390*	30 639 ± 4459*
6 days
0	7442 ± 59	160 ± 76	4064 ± 69	3343 ± 155	214 ± 69
0.05	7432 ± 374	846 ± 124*	4057 ± 261	6941 ± 359*	5149 ± 325*
0.1	7971 ± 278	255 ± 16	9114 ± 310*	5941 ± 398*	2398 ± 80*
0.25	7442 ± 394	2779 ± 194*	8739 ± 239*	4146 ± 68*	1624 ± 372*
0.5	7471 ± 187	427 ± 167	11 306 ± 370*	8437 ± 39*	1754 ± 219*
1	7898 ± 305	2341 ± 119*	21 896 ± 563*	9385 ± 393*	5248 ± 122*
2.5	12 643 ± 449*	25 341 ± 635*	26 080 ± 960*	22 685 ± 796*	17 777 ± 791*
5	6471 ± 203*	34 027 ± 586*	33 038 ± 2129*	25 531 ± 312*	23 356 ± 60*9

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates a significant change in secretion compared to control cells (cells treated with vehicle alone), p < 0.05.

Table 6. Effects of HBCD exposures on IL -1β secretion from PBMC.

[HBCD] μM	F 186	F 187	F 189	F 192	F 193	F 195
24 h
0	4400 ± 60	2084 ± 163	10 622 ± 73	25 839 ± 700	8122 ± 414	35 872 ± 1059
0.05	3373 ± 136*	3343 ± 134*	11 815 ± 341*	15 312 ± 631*	9143 ± 321*	34 858 ± 601
0.1	3753 ± 168*	3607 ± 170*	17 260 ± 501*	13 258 ± 455*	10 046 ± 402*	31 956 ± 518*
0.25	3620 ± 53*	5406 ± 122*	16 084 ± 350*	23 968 ± 551*	10 299 ± 221*	30 442 ± 507*
0.5	7840 ± 156*	7699 ± 291*	17 985 ± 512*	19 312 ± 759*	9295 ± 300*	40 789 ± 1326*
1	10 880 ± 72*	11 814 ± 249*	18 616 ± 299*	28 269 ± 385*	12 214 ± 555*	47 844 ± 827*
2.5	28 253 ± 1612*	9894 ± 258*	36 359 ± 386*	17 925 ± 726*	24 105 ± 77*	52 456 ± 994*
5	35 667 ± 200*	38 814 ± 690*	37 014 ± 713*	25 204 ± 1029	29 117 ± 2594*	68 594 ± 2789*
48 h
0	1152 ± 9	2196 ± 121	5919 ± 76	19 302 ± 707	13 039 ± 114	57 079 ± 2453
0.05	5665 ± 250*	3804 ± 245*	7616 ± 11*	20 389 ± 371	16 137 ± 486*	41 769 ± 1231*
0.1	5456 ± 430*	1522 ± 178*	9302 ± 802*	25 433 ± 338*	17 501 ± 216*	51 914 ± 1988
0.25	2892 ± 77*	3601 ± 263*	9127 ± 165*	22 723 ± 842*	17 160 ± 586*	56 190 ± 2135
0.5	4051 ± 36*	3130 ± 132*	11 142 ± 698*	27 126 ± 1121	18 910 ± 640*	48 895 ± 2519
1	2438 ± 187*	3051 ± 160*	12 767 ± 110*	29 819 ± 692*	18 849 ± 365*	58 535 ± 1045
2.5	7994 ± 356*	44 790 ± 174*	24 089 ± 913*	31 846 ± 856*	25 849 ± 949*	75 163 ± 3235*
5	10 803 ± 44*	47 326 ± 247*	21 309 ± 464*	25 205 ± 619*	29 743 ± 112*	77 508 ± 2747*
6 days
0	1871 ± 115	1607 ± 31	4475 ± 472	14 638 ± 723	15 437 ± 2265	26 787 ± 116
0.05	2790 ± 83*	1213 ± 121*	7706 ± 315*	15 143 ± 946	19 419 ± 615	27 471 ± 1050
0.1	2224 ± 45*	1347 ± 212	6955 ± 215*	14 851 ± 562	30 307 ± 679*	28 505 ± 1530
0.25	3138 ± 57*	2213 ± 83*	10 921 ± 178*	17 164 ± 774*	19 511 ± 1020	25 297 ± 1050
0.5	4674 ± 191*	5547 ± 210*	9492 ± 206*	15 416 ± 202	24 030 ± 1278*	32 012 ± 210*
1	4179 ± 109*	7920 ± 200*	17 932 ± 1245*	16 053 ± 379	22 604 ± 2341*	30 210 ± 525*
2.5	13 553 ± 568*	32 833 ± 234*	25 689 ± 801*	16 921 ± 105*	29 622 ± 2310*	22 715 ± 289*
5	17 936 ± 528*	36 760 ± 1513*	22 859 ± 207*	21 063 ± 959*	31 604 ± 1640*	44 336 ± 657

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates a significant change in secretion compared to control cells (cells treated with vehicle alone), p < 0.05.

Figure 3. Effects of 24-h exposure to HBCD on IL-1β secretion from monocyte-depleted PBMC pre-treated with selective enzyme inhibitors. Data shown is based on cells from an individual donor. (a) Caspase I inhibitor II (Caspase I) (donor F 267). (b) NF-κB inhibitor (BAY 11-7085) (donor F275). (c) JNK inhibitor (donor F271). (d) MEK1/2 (ERK1/2 pathway) inhibitor (PD98059) (donor F267). (e) p38 inhibitor (SB202190) (donor F255). * Value significantly different from control cells with vehicle alone at p < 0.05. ** Value significantly different from control + inhibitor at p < 0.05.

Figure 4. Signaling cascade involved in IL-1β secretion.

Table 7. Effects of 24 h exposure to HBCD ± pathway inhibitors on IL-1β secretion from MD-PBMC.

[HBCD] μM	F253	F254	F263	F267	F268	F271	F278	F289	F293
24 h: Caspase-1 inhibitor II
0	230 ± 19	156 ± 87	910 ± 36	4745 ± 312	10 778 ± 352	1595 ± 201	1198 ± 7	4480 ± 461	925 ± 82
0 + CI	48 ± 38*	33 ± 28	261 ± 39*	725 ± 131*	2599 ± 60*	382 ± 128*	1669 ± 211	1947 ± 177*	211 ± 83*
0.5	373 ± 7*	2187 ± 70*	2620 ± 105*	7408 ± 205*	12 489 ± 344*	1808 ± 242	2092 ± 75*	3598 ± 215	1901 ± 122*
0.5 + CI	65 ± 62	4187 ± 114**	1116 ± 48**	1360 ± 14**	1847 ± 162**	3202 ± 75**	1516 ± 103	926 ± 58**	75 ± 30**
1	571 ± 26*	3295 ± 30*	1374 ± 18*	13 102 ± 1502*	15 274 ± 295*	4191 ± 138*	1692 ± 170*	5990 ± 198*	2881 ± 41*
1 + CI	61 ± 22	2085 ± 28**	1626 ± 53**	2126 ± 104**	2839 ± 249	2387 ± 317**	1449 ± 7	0 ± 41**	401 ± 21**
2.5	6019 ± 627*	6636 ± 370*	15 061 ± 456*	22 781 ± 670*	25 957 ± 1077*	17 437 ± 951*	6375 ± 404*	18 969 ± 1107*	7037 ± 314*
2.5 + CI	301 ± 62	3295 ± 30**	1600 ± 48**	7654 ± 335**	7115 ± 254**	6612 ± 525**	1810 ± 78	3603 ± 490**	1571 ± 158**

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates significant change in secretion compared to control cells (cells treated with vehicle alone) at p < 0.05.

** Indicates significant increase compared to no HBCD + inhibitor (0 + I) at p < 0.05.

Table 8. Effects of 24 h exposure to HBCD ± pathway inhibitors on IL-1β secretion from MD-PBMC.

[HBCD]μM	F275	F276	F278	F 289	F 293
24 h: NF-κB inhibitor (BAY 11-7085)
0	828 ± 76	9730 ± 190	10 513 ± 472	3818 ± 185	1271 ± 21
0 + B	1833 ± 409*	2716 ± 25*	2313 ± 62*	2937 ± 189*	513 ± 42*
0.5	2269 ± 59*	5875 ± 354*	11 821 ± 540*	3608 ± 72	1583 ± 122*
0.5 + B	2627 ± 123	1854 ± 88	2790 ± 378	2921 ± 81**	1221 ± 43
1	3549 ± 346*	8919 ± 177*	5380 ± 178*	3793 ± 222	2523 ± 46*
1 + B	3220 ± 132**	2716 ± 402	3903 ± 317	3217 ± 106	1520 ± 90**
2.5	11 186 ± 302*	23 455 ± 1383*	35 533 ± 678*	12 226 ± 2170*	6060 ± 231*
2.5 + B	4436 ± 148**	4607 ± 448**	14 292 ± 377**	10 394 ± 56	3913 ± 134**

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates significant change in secretion compared to control cells (cells treated with vehicle alone) at p < 0.05.

** Indicates significant increase compared to no HBCD + inhibitor (0 + I) at p < 0.05.

Table 9. Effects of 24 h exposure to HBCD ± pathway inhibitors on IL-1β secretion from MD-PBMC.

[HBCD] μM	F 271	F275	F278	F289	F293
24 h: JNK Inhibitor X BI78D3
0	1220 ± 75*	1455 ± 218	1339 ± 214	4060 ± 137	1447 ± 77
0 + J	649 ± 98	2113 ± 413	2979 ± 270*	4829 ± 111*	1321 ± 108
0.5	2796 ± 98*	1722 ± 88	2953 ± 228*	3874 ± 67	2152 ± 243*
0.5 + J	2818 ± 210**	1305 ± 43	2867 ± 215	3560 ± 249	2089 ± 121**
1	4389 ± 59*	1730 ± 43	2520 ± 156*	3697 ± 92*	2215 ± 58*
1 + J	2645 ± 94**	1955 ± 109	3553 ± 140**	11 550 ± 170**	2401 ± 115**
2.5	17 887 ± 786*	9805 ± 676*	10 190 ± 844*	14 325 ± 493*	8612 ± 414*
2.5 + J	9710 ± 424**	7547 ± 559**	9187 ± 621**	18 290 ± 906**	5810 ± 211**

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates significant change in secretion compared to control cells (cells treated with vehicle alone) at p < 0.05.

** Indicates significant increase compared to no HBCD + inhibitor (0 + I) at p < 0.05.

Table 10. Effects of 24 h exposure to HBCD ± pathway inhibitors on IL-1β secretion from MD-PBMC.

[HBCD] μM	F253	F254	F255	F263	F265	F 267	F268
24 h: ERK 1/2 pathway inhibitor (PD98059)
0	44 ± 23	987 ± 20	948 ± 33	373 ± 40	211 ± 37	4528 ± 199	9812 ± 394
0 + PD	164 ± 52*	3410 ± 314*	1699 ± 22*	392 ± 42	232 ± 85*	5344 ± 184 *	10 691 ± 584*
0.5	2293 ± 234*	5554 ± 105*	6235 ± 57*	1907 ± 103*	854 ± 85*	12 823 ± 164*	15 093 ± 169*
0.5 + PD	1845 ± 97**	5070 ± 415**	9044 ± 436**	1253 ± 89**	488 ± 92**	6738 ± 163**	10 900 ± 241
1	2044 ± 180*	5659 ± 590*	5392 ± 18*	2095 ± 112*	2244 ± 76*	13 007 ± 206*	15 418 ± 655*
1 + PD	2572 ± 40**	5184 ± 365**	6302 ± 150**	2111 ± 72**	1663 ± 75**	8310 ± 281**	12 772 ± 435**
2.5	5696 ± 242*	4988 ± 223*	7159 ± 97*	2944 ± 126*	14 589 ± 384*	18 644 ± 1330*	28 358 ± 1979
2.5 + PD	4029 ± 95**	7164 ± 546*	8258 ± 92**	13 395 ± 1356**	13 187 ± 966**	12 823 ± 741**	19 053 ± 1340**

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates significant change in secretion compared to control cells (cells treated with vehicle alone) at p < 0.05.

** Indicates significant increase compared to no HBCD + inhibitor (0 + I) at p < 0.05.

Table 11. Effects of 24 h exposure to HBCD ± pathway inhibitors on IL-1β secretion from MD-PBMC.

[HBCD] μM	F253	F254	F255	F263	F265	F267
24 h: p38 pathway inhibitor (SB202190)
0	401 ± 28	375 ± 21	366 ± 91	613 ± 146	169 ± 11	5739 ± 78
0 + SB	1943 ± 375*	1408 ± 299*	1038 ± 33*	799 ± 67	1228 ± 93*	5910 ± 111
0.5	5145 ± 594*	4622 ± 72*	1285 ± 126*	2767 ± 101*	1555 ± 23*	10 061 ± 190*
0.5 + SB	5264 ± 430**	5805 ± 222**	2704 ± 51**	3318 ± 173**	925 ± 103**	9636 ± 101**
1	3561 ± 320*	3513 ± 95*	1483 ± 126*	2256 ± 135*	747 ± 16*	21 061 ± 544*
1 + SB	5315 ± 78**	5047 ± 182**	2699 ± 41**	3793 ± 259**	1233 ± 32	9739 ± 331**
2.5	3925 ± 60*	3351 ± 313*	4017 ± 61*	8705 ± 609*	3454 ± 56*	25 332 ± 1274*
2.5 + SB	5319 ± 297**	6190 ± 95**	2467 ± 103**	4554 ± 358**	929 ± 34**	25 498 ± 509**

Values are means (pg/ml) ± SD of triplicate determinations.

* Indicates significant change in secretion compared to control cells (cells treated with vehicle alone) at p < 0.05.

** Indicates significant increase compared to no HBCD + inhibitor (0 + I) at p < 0.05.