Figure 3. The selective β2-AR agonist bambuterol ameliorates the severity and fatality of acute GvHD.

(A) Body weight, clinical score, and survival of lethally irradiated BALB/c mice after allo-HCT with 3.5 × 10⁶ WT C57BL/6 TCD-BM alone or combined with 0.7 × 10⁶ WT C57BL/6 pan–T cells treated with daily injections of saline and bambuterol. Data pooled from 2 individual experiments; n = 6–8 per group for a total of n = 12–16 per group. (B) Body weight, clinical score, and survival of lethally irradiated C3H/SW mice after allo-HCT with 3.5 × 10⁶ WT C57BL/6 TCD-BM alone or combined with 1.5 × 10⁶ WT C57BL/6 pan–T cells treated with daily injections of saline and bambuterol. Data pooled from 2 individual experiments; n = 4–7 per group for a total of n = 8–14 per group. Bambuterol significantly ameliorated aGvHD in the MHC and miHA mismatched models, as assessed by weight loss, clinical score, and survival. (C) T-bet⁺, Foxp-3⁺, IFN-γ⁺, IL-17⁺, and IL-10⁺ frequencies in CD4⁺ T cells within single live H-2^b+H-2^d–CD45⁺CD3⁺ cell populations from spleen and liver of mice 7 and 14 days after allo-HCT in the B6→BALB/c model transplanted with 3.5 × 10⁶ WT C57BL/6 TCD-BM combined with 0.7 × 10⁶ WT C57BL/6 pan–T cells treated with daily injections of saline and bambuterol at ST. Data pooled from 2 individual experiments; total n = 5–6 per group. There were significantly increased CD4⁺Foxp-3⁺ and CD4⁺IL-10⁺ and decreased CD4⁺T-bet⁺, CD4⁺IFN-γ⁺, and CD4⁺IL-17⁺ populations in the bambuterol-treated recipients. For comparison of survival curves, a log-rank (Mantel-Cox) test was used in A and B. For comparison of the means, an unpaired 2-tailed t test was used in C. Two-way ANOVA with Tukey’s multiple comparisons test was used for body weight and clinical score difference in A and B. *P < 0.05, **P < 0.01, ***P < 0.001. Body weight, clinical score, and survival data are shown as means ± SEM. Other data are presented as median ± min to max.