Figure 5.
Treatment with anti-IL-18 mAb attenuates acute GVHD-related mortality and morbidity. (A) bm1 and bm12 animals underwent irradiation and transplantation with 5 × 106 TCD BM cells and 2 × 106 CD8+ and CD4+ T cells, respectively, from allogeneic B6 or syngeneic bm1 and bm12 donors, as described in “Materials and methods.” Serum from these recipient animals (n = 4/group), was obtained on day 7 after BMT and was analyzed as described in “Materials and methods.” Allogeneic bm12 (▪) and bm1 recipients (▤) and syngeneic (□) animals are shown. Serum IL-18 levels are elevated after allogeneic BMT. (B) bm1 recipients were given 13 Gy TBI and underwent transplantation with 5 × 106 TCD BM and 3 × 106 CD8+ cells from B6 donors, as in Figure 1B. Allogeneic recipient animals were injected intraperitoneally with 10 μg/d anti-IL-18 mAb (▪, n = 14) or the isotype IgG2a (□, n = 14) from day -1, 0, and every 3 days thereafter until the third week (total, 9 doses). Syngeneic recipients (▵, n = 6) underwent transplantation with cells from bm1 donors and were injected with the isotype IgG2a following the same schedule. Data of 2 individual experiments are combined. (B) Percentage survival after BMT. ▪ vs □; P = .01 by Wilcoxon rank test. (C) Animals were scored for clinical GVHD, as described in “Materials and methods.” ▪ vs □; ★P < .01 or ★★P < .05 by Mann-Whitney U test. Error bars represent ± SE.