ICA reduces GVHD-related morbidity and mortality in a dose-dependent manner in allo-BMT recipients. (A-G) B10.BR recipients were lethally irradiated and subjected to allo-BMT with TCD-BM alone or in combination with purified T cells (TCD-BM + T) from C57Bl/6 donor mice to induce GVHD. Mice received daily oral gavage with 100 mg/kg or 150 mg/kg ICA or vehicle (VEH) starting 1 day prior to irradiation. All data from day 21 posttransplant. Representative data from 2 experimental repeats at each ICA dose; n = 15 to 20 per group, 5 mice censored per condition on day 21 for various assays. (A) Weight loss (n = 15-20). (B) Kaplan-Meier survival curve (n = 15-20) with ticks indicating mice censored for histological studies. (C) Hematoxylin and eosin (H&E) staining of distal colon in animals receiving 100 mg/kg ICA or VEH. (All images are ×200 magnification; “L” indicates the lumen). (D-F) Quantitation of colon histology. For each parameter, an average value per mouse was determined as detailed in supplemental Methods (n = 4 to 8 per condition). (D) Degree of crypt loss (0 = none → 3 = severe). (E) Apoptotic cells per crypt. (F) Degree of infiltrating immune cells (0 = none → 3 = severe). (G) Quantitation of CFU per gram MLN. (H) Image of representative result of dilution plating of MLN homogenates to determine CFU/g MLN. (I) TER measured across Caco-2 cell monolayers after treatment with increasing concentrations of ICA. Combined data from 3 experiments. (J) TER measured across Caco-2 cell monolayers damaged with TNF-α and treated with ICA (100 µM). Combined data from 2 experiments. Statistics: Mantel Cox Log-rank (survival curve), ANOVA. ****P < .0001; ***P = .0001 to .001; **P = .001 to .01; *P = .01 to .05.