Table 1.
Effects of anti-TWEAK monoclonal antibodies on the secretion of proinflammatory molecules by dermal fibroblasts stimulated by hTWEAK, alone or in association with TNF or IL-1β
| BCB10 | BEB3 | Stimulation | BCB10 | BEB3 | Stimulation | |||
| Stimulus | None | (10 μg/ml) | (10 μg/ml) | index* | None | (10 μg/ml) | (10 μg/ml) | index* |
| IL-8 secretion (ng/ml) | IL-6 secretion (ng/ml) | |||||||
| Medium alone | 6.4 | 8.3 | 5.4 | 1.0 | 1.1 | 1.4 | 0.9 | 1.0 |
| hTWEAK (50 ng/ml) | 55.1 | 9.6 | 96.0 | 17.8 | 6.0 | 2.2 | 15.9 | 17.7 |
| TNF (1 ng/ml) | 111.6 | 126.1 | 114.3 | 1.0 | 11.2 | 11.4 | 10.8 | 1.0 |
| TNF + hTWEAK | 264.3 | 136.7 | 446.1 | 3.9 | 21.1 | 13.9 | 42.9 | 4.0 |
| IL-1β (0.1 ng/ml) | 214.9 | 248.6 | 190.2 | 1.0 | 42.5 | 60.9 | 53.5 | 1.0 |
| IL-1β + hTWEAK | 439.7 | 277.2 | 583.1 | 3.1 | 69.8 | 59.3 | 116.8 | 2.2 |
| MMP-1 secretion (μg/ml) | IP-10 secretion (pg/ml) | |||||||
| Medium alone | 0.44 | 0.53 | 0.38 | 1.0 | 18.5 | nd | nd | 1.0 |
| hTWEAK (50 ng/ml) | 1.68 | 0.82 | 2.46 | 6.5 | 388 | nd | 625 | 33.8 |
| TNF (1 ng/ml) | 2.36 | 2.52 | 2.49 | 1.0 | 241 | 85 | 93 | 1.0 |
| TNF + hTWEAK | 2.38 | 3.09 | 3.20 | 1.3 | 6358 | 600 | 6403 | 68.8 |
| IL-1β (0.1 ng/ml) | 2.48 | 2.82 | 2.05 | 1.0 | 175 | 103 | 111 | 1.0 |
| IL-1β + hTWEAK | 3.8 | 2.89 | 3.59 | 1.8 | 272 | 83 | 407 | 3.7 |
| PGE2 secretion (ng/ml) | RANTES secretion (ng/ml) | |||||||
| Medium alone | 15 | 11 | 10 | 1.0 | 0.79 | 0.63 | 0.55 | 1.0 |
| hTWEAK (50 ng/ml) | 22 | 8 | 31 | 3.1 | 10.56 | 0.77 | 15.72 | 28.6 |
| TNF (1 ng/ml) | 71 | 41 | 57 | 1.0 | 2.04 | 2.65 | 1.99 | 1.0 |
| TNF + hTWEAK | 125 | 104 | 177 | 3.1 | 77.88 | 5.27 | 91.96 | 46.2 |
| IL-1β (0.1 ng/ml) | 139 | 156 | 259 | 1.0 | 1.16 | 1.30 | 1.49 | 1.0 |
| IL-1β + hTWEAK | 143 | 186 | 312 | 1.2 | 29.28 | 1.57 | 51.78 | 34.7 |
* Stimulationindices were calculated from the values obtained with the BEB3 anti-TWEAK mAb results: TWEAK/medium; (TNF + TWEAK)/TNF alone; (IL-1β + TWEAK)/IL-1β alone. Similar results were obtained in 3 independent experiments. hTWEAK, human TNF-like weak inducer of apoptosis; IP-10, interferon-γ-inducible protein-10; MMP-1, matrix metalloproteinase-1; nd, not detectable; PGE2, prostaglandin E2; RANTES, regulated on activation, normal T expressed and secreted; TNF, tumour necrosis factor.