Figure 1. Proinflammatory IL-1β has effects on both T cells and DCs while receptor antagonism or depletion reduces acute GvHD related mortality. (A) BALB/c mice underwent TBI followed by transplantation with C57/BL6 BM alone (n = 10) or C57/BL6 BM plus T cells, and were monitored for survival. Where indicated, mice received either vehicle (PBS; n = 16) or Anakinra (n = 10 per group). Treatment was started on day −1 or +5, as indicated. The experiment was performed twice and the resulting survival data were pooled. (B) C57BL/6 mice underwent TBI followed by i.v. injection of C3H BM alone or C3H BM plus T cells and were monitored for survival. Where indicated, mice received either no treatment or an antagonistic anti–IL-1β antibody on day −1 or +5. The experiment was performed twice, and the resulting survival data were pooled. Survival of mice receiving anti–IL-1β antibody on day −1 versus day +5: P < 0.0001; n = 10 per group. (C) BALB/c mice underwent TBI followed by allo-HCT with C57/BL6 BM plus T cells. Expression of IL-1R on splenic donor type (H-2Kb+) CD4+, CD8+, and CD11c+ cells was analyzed by flow cytometry at the indicated time points after allo-HCT. Mean fluorescence intensity (MFI) is displayed for day 3 (filled square) and for day 10 (filled triangle) compared with the untreated group (open circle). Each data point represents an individual animal (n = 6 per group). The experiment was repeated twice and the resulting data were pooled. (D) BALB/c mice received TBI + C57/BL6 BM alone or with T cells from IL-1R+/+ (open circle) or IL-1R−/− (filled square) donors and were monitored for survival. The experiment was performed twice and the resulting survival data were pooled. IL-1R+/+ T cells versus IL-1R−/− T cells: P = 0.0102; n = 10 per group. (E) C57BL/6 mice underwent TBI followed by transplantation with BALB/c BM alone (n = 3) or BALB/c BM plus T cells (n = 10 per group). Mice that received T cells were additionally injected i.v. with DCs from IL-1R+/+ C57BL/6 mice (open circle) or DCs from IL-1R−/− C57BL/6 mice (filled square) on day 0. The experiment was performed twice, and the resulting survival data were pooled. DC IL-1R+/+ versus DC IL-1R−/−: P = 0.0002. ***, P < 0.0001; **, P < 0.001; *, P < 0.05.
Figure 1.

Proinflammatory IL-1β has effects on both T cells and DCs while receptor antagonism or depletion reduces acute GvHD related mortality. (A) BALB/c mice underwent TBI followed by transplantation with C57/BL6 BM alone (n = 10) or C57/BL6 BM plus T cells, and were monitored for survival. Where indicated, mice received either vehicle (PBS; n = 16) or Anakinra (n = 10 per group). Treatment was started on day −1 or +5, as indicated. The experiment was performed twice and the resulting survival data were pooled. (B) C57BL/6 mice underwent TBI followed by i.v. injection of C3H BM alone or C3H BM plus T cells and were monitored for survival. Where indicated, mice received either no treatment or an antagonistic anti–IL-1β antibody on day −1 or +5. The experiment was performed twice, and the resulting survival data were pooled. Survival of mice receiving anti–IL-1β antibody on day −1 versus day +5: P < 0.0001; n = 10 per group. (C) BALB/c mice underwent TBI followed by allo-HCT with C57/BL6 BM plus T cells. Expression of IL-1R on splenic donor type (H-2Kb+) CD4+, CD8+, and CD11c+ cells was analyzed by flow cytometry at the indicated time points after allo-HCT. Mean fluorescence intensity (MFI) is displayed for day 3 (filled square) and for day 10 (filled triangle) compared with the untreated group (open circle). Each data point represents an individual animal (n = 6 per group). The experiment was repeated twice and the resulting data were pooled. (D) BALB/c mice received TBI + C57/BL6 BM alone or with T cells from IL-1R+/+ (open circle) or IL-1R−/− (filled square) donors and were monitored for survival. The experiment was performed twice and the resulting survival data were pooled. IL-1R+/+ T cells versus IL-1R−/− T cells: P = 0.0102; n = 10 per group. (E) C57BL/6 mice underwent TBI followed by transplantation with BALB/c BM alone (n = 3) or BALB/c BM plus T cells (n = 10 per group). Mice that received T cells were additionally injected i.v. with DCs from IL-1R+/+ C57BL/6 mice (open circle) or DCs from IL-1R−/− C57BL/6 mice (filled square) on day 0. The experiment was performed twice, and the resulting survival data were pooled. DC IL-1R+/+ versus DC IL-1R−/−: P = 0.0002. ***, P < 0.0001; **, P < 0.001; *, P < 0.05.

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