Table 4.
IL-8 release from human PBMC stimulated in vitro for 24, 48 and 72 h with 1 μg well−1 of indicated therapeutic mAbs in aqueous and solid phase. Cytokine release was measured by ELISA. The lectin PHA at 10 μg ml−1 was used as mitogen control. All responses were compared with IgG1 isotype control with the exception of TGN1412 and natalizumab which were compared with IgG4κ isotype control. Group responses shown are geometric mean followed by 95% confidence interval in brackets. Significant results are shown in bold (repeated measures analysis of log10 transformed data using Dunnett's method and 95% confidence). Donor responses shown (n = 7–16) are from 2–4 independent experiments
| Therapeutic mAb | Aqueous phase IL-8 release at: | Solid phase Il-8 release at: | ||||
|---|---|---|---|---|---|---|
| 24 h | 48 h | 72 h | 24 h | 48 h | 72 h | |
| IgG1 control | 275 pg ml−1 (89, 855) | 416 pg ml−1 (129, 1 346) | 724 pg ml−1 (256, 2 045) | 16 862 pg ml−1 (10 974, 25 909) | 25 089 pg ml−1 (15 365, 40 967) | 33 284 pg ml−1 (20 478, 54 100) |
| IgG4 control | 470 pg ml−1 (206, 1 070) | 845 pg ml−1 (489, 1 459) | 502 pg ml−1 (167, 1 511) | 764 pg ml−1 (230, 2 542) | 1 001 pg ml−1 (280, 3 583) | 960 pg ml−1 (341, 2 707) |
| Natalizumab | 66 pg ml−1 (43.4, 99.5) | 245 pg ml−1 (90.8, 658) | 326 pg ml−1 (109, 976) | 107 pg ml−1 (54.3, 211) | 118 pg ml−1 (58.5, 238) | 121 pg ml−1 (65.8, 224) |
| Adalimumab | 59.4 pg ml−1 (40.9, 86.2) | 50.0 pg ml−1 (50.0, 50.0) | 71.2 pg ml−1 (47.4, 107) | 16 061 pg ml−1 (9 049, 28 507) | 24 209 pg ml−1 (11 809, 49 631) | 30 220 pg ml−1 (12 838, 71 133) |
| Infliximab | 50.0 pg ml−1 (50.0, 50.0) | 69.2 pg ml−1 (42.8, 112) | 85.5 pg ml−1 (37.8, 193) | 18 816 pg ml−1 (10 358, 34 180) | 26 130 pg ml−1 (13 012, 52 474) | 30 838 pg ml−1 (15 075, 63 083) |
| Etanercept | 71.3 pg ml−1 (47.1, 108) | 80.6 pg ml−1 (39.5, 164) | 66.0 pg ml−1 (41.9, 104) | 3 495 pg ml−1 (1 655, 7 381) | 4 416 pg ml−1 (1 731, 11 267) | 4 197 pg ml−1 (1 482, 11 886) |
| Basiliximab | 135 pg ml−1 (47.0, 387) | 150 pg ml−1 (64.1, 352) | 785 pg ml−1 (363, 1 702) | 12 231 pg ml−1 (7 793, 19 197) | 18 684 pg ml−1 (11 695, 29 849) | 21 788 pg ml−1 (12 617, 37 627) |
| Daclizumab | 60.3 pg ml−1 (44.7, 81.3) | 193 pg ml−1 (74.1, 500) | 1 336 pg ml−1 (706, 2 530) | 19 556 pg ml−1 (13 764, 27 785) | 29 025 pg ml−1 (18 947, 44 465) | 35 308 pg ml−1 (21 726, 57 380) |
| Bevacizumab | 70.6 pg ml−1 (44.1, 113) | 229 pg ml−1 (86.3, 606) | 1 198 pg ml−1 (518, 2 772) | 28 368 pg ml−1 (20 021, 40 196) | 43 355 pg ml−1 (28 858, 65 137) | 53 843 pg ml−1 (34 771, 83 375) |
| Trastuzumab | 86.2 pg ml−1 (50.9, 146) | 217 pg ml−1 (93.9, 501) | 911 pg ml−1 (405, 2 052) | 14 410 pg ml−1 (4 501, 46 129) | 39 916 pg ml−1 (29 875, 53 332) | 48 426 pg ml−1 (35 804, 65 498) |
| Rituximab | 222 pg ml−1 (72.7, 678) | 523 pg ml−1 (160, 1 708) | 832 pg ml−1 (288, 2 405) | 13 649 pg ml−1 (4 347, 42 852) | 36 294 pg ml−1 (28 656, 45 968) | 41 739 pg ml−1 (30 839, 56 492) |
| Alemtuzumab | 4 551 pg ml−1 (2 264, 9 146) | 6 050 pg ml−1 (3 719, 9 842) | 11 595 pg ml−1 (7 152, 18 799) | 15 276 pg ml−1 (4 689, 49 766) | 40 659 pg ml−1 (30 677, 53 890) | 45 493 pg ml−1 (35 229, 58 747) |
| Muromonab-CD3 | 7 115 pg ml−1 (2 865, 17 671) | 9 231 pg ml−1 (5 839, 14 595) | 11 355 pg ml−1 (8 007, 16 102) | 18 052 pg ml−1 (12 296, 26 504) | 40 426 pg ml−1 (25 755, 63 453) | 54 846 pg ml−1 (34 370, 87 520) |
| TGN1412 | 508 pg ml−1 (165, 1 565) | 1 266 pg ml−1 (409, 3 920) | 1 220 pg ml−1 (394, 3 779) | 14 137 pg ml−1 (9 347, 21 382) | 36 431 pg ml−1 (23 768, 55 842) | 46 037 pg ml−1 (33 392, 63 471) |
| Mitogen | 25 720 pg ml−1 (10 267, 64 431) | 65 723 pg ml−1 (29 621, 145 827) | 80 929 pg ml−1 (37 229, 175 925) | 20 577 pg ml−1 (10 110, 41 879) | 103 293 pg ml−1 (61 336, 173 949) | 107 001 pg ml−1 (72 335, 158 280) |