IL-18 increases GVHD-specific morbidity and target organ damage after MHC class I disparate BMT. (A) bm1 animals underwent irradiation and transplantation with 5 × 106 TCD BM cells and 2 × 106 CD8+ T cells from allogeneic B6 or syngeneic bm1 donors, as described in “Materials and methods.” IL-18 was injected into syngeneic (▴) and allogeneic recipients (•), and allogeneic control mice (○) were injected with the diluent. The animals were assessed weekly for clinical severity of acute GVHD. Data from 1 of 2 similar experiments are shown. Clinical severity was increased with the injection of IL-18. ○ vs •; ★P < .01 or ★★P < .05 by Mann-Whitney U test. (B) Serum from the recipient animals that underwent transplantation, as described (n = 4 per group), was obtained on day 7 after BMT and was analyzed. Allogeneic recipients treated with IL-18 (▤) or diluent (▪) and IL-18-injected syngeneic (□) animals are shown. Serum LPS levels are elevated after IL-18 treatment. ▤ vs ▪; ★P < .001. Results from 1 of 2 similar experiments are shown. (C) Animals that underwent transplantation (n = 4/group) were killed; small and large bowels were obtained for analysis on day 7 after BMT. Coded slides were scored semiquantitatively to assess pathologic damage, as described in “Materials and methods.” Total GVHD score; mean ± SE of the sum of scores for small bowel and colon from individual animals in each group. Allogeneic recipients treated with IL-18 (▤) or diluent (▪) and IL-18-injected syngeneic (□) animals are shown. ▤ vs ▪; ★P = .002. ▪ vs □; P = .01.
