Figure 1.
Administering rLIF ameliorates GVHD in mice. (A) Serum LIF levels in B6C3F1 (left) and C57BL/6 (right) mice at different days (D) after TBI (2 × 5.5 Gy), syngeneic BM + T, allogenic BM, and allogenic BM + T. n ≥ 3 mice/group (each dot represents a mouse). Serum LIF levels were measured by ELISAs. (B) The serum LIF levels at 2 days after allo-BMT were positively correlated with the survival length of mice after allo-BMT. B6C3F1 mice were exposed to 2 × 5.5 Gy TBI, followed by transplantation of BM and T cells from C57BL/6 mice. (C) Lethally irradiated B6C3F1 mice received BM alone (BM; n = 3), BM and T cells from C57BL/6 mice (BM + T; n = 13), or BM and T cells along with rLIF treatment (IP, 30 ng/g body weight, twice a day for the period as indicated) (BM + T + rLIF; n = 10 for D-4 to D3; n = 8 for D1 to D3 and D8 to D10). Schematic diagram of experimental procedures is shown on the upper left. Three panels shown are Kaplan-Meier survival curves (upper right), weight loss (lower left), and GVHD score (lower right) of mice after allo-BMT. (D) Lethally irradiated C57BL/6 mice received BM (n = 3), BM + T from BALB/c mice (n = 12), or BM + T + rLIF (n = 9). Mice were treated with rLIF as follows: IP, 30 ng/g body weight, twice a day for 7 days (D-4 to D3). Three panels shown are Kaplan-Meier survival curves (left), weight loss (middle), and GVHD score (right) of mice after allo-BMT. (E,F) Tissues from lethally irradiated B6C3F1 mice receiving C57BL/6 BM (n = 4), BM + T (n = 8) or BM + T + rLIF (n = 8). Tissues from these mice were collected at 14 days after allo-BMT for histopathologic analysis. (E) Representative hematoxylin and eosin–stained images of SI, colon, and liver tissues. (F) The clinical score was analyzed as described in Methods to reflect the histopathologic damage in different tissues. (G) Lethally irradiated C57BL/6 wild-type (n = 11) and LIF knockout (n = 7) mice received BM + T from BALB/c mice. Kaplan-Meier survival curves (upper) and GVHD score (lower) of mice after allo-BMT are presented. Data presented are from at least 3 independent experiments. (A,F) Data are presented as mean ± standard deviation; (C-D,G) data are presented as mean ± standard error of the mean. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, n.s.: not significant; unpaired t test with Welch’s correction (A,F), Spearman’s correlation (B), Kaplan-Meier survival analysis for survival, and analysis of variance for analysis of weight loss and GVHD score.

Administering rLIF ameliorates GVHD in mice. (A) Serum LIF levels in B6C3F1 (left) and C57BL/6 (right) mice at different days (D) after TBI (2 × 5.5 Gy), syngeneic BM + T, allogenic BM, and allogenic BM + T. n ≥ 3 mice/group (each dot represents a mouse). Serum LIF levels were measured by ELISAs. (B) The serum LIF levels at 2 days after allo-BMT were positively correlated with the survival length of mice after allo-BMT. B6C3F1 mice were exposed to 2 × 5.5 Gy TBI, followed by transplantation of BM and T cells from C57BL/6 mice. (C) Lethally irradiated B6C3F1 mice received BM alone (BM; n = 3), BM and T cells from C57BL/6 mice (BM + T; n = 13), or BM and T cells along with rLIF treatment (IP, 30 ng/g body weight, twice a day for the period as indicated) (BM + T + rLIF; n = 10 for D-4 to D3; n = 8 for D1 to D3 and D8 to D10). Schematic diagram of experimental procedures is shown on the upper left. Three panels shown are Kaplan-Meier survival curves (upper right), weight loss (lower left), and GVHD score (lower right) of mice after allo-BMT. (D) Lethally irradiated C57BL/6 mice received BM (n = 3), BM + T from BALB/c mice (n = 12), or BM + T + rLIF (n = 9). Mice were treated with rLIF as follows: IP, 30 ng/g body weight, twice a day for 7 days (D-4 to D3). Three panels shown are Kaplan-Meier survival curves (left), weight loss (middle), and GVHD score (right) of mice after allo-BMT. (E,F) Tissues from lethally irradiated B6C3F1 mice receiving C57BL/6 BM (n = 4), BM + T (n = 8) or BM + T + rLIF (n = 8). Tissues from these mice were collected at 14 days after allo-BMT for histopathologic analysis. (E) Representative hematoxylin and eosin–stained images of SI, colon, and liver tissues. (F) The clinical score was analyzed as described in Methods to reflect the histopathologic damage in different tissues. (G) Lethally irradiated C57BL/6 wild-type (n = 11) and LIF knockout (n = 7) mice received BM + T from BALB/c mice. Kaplan-Meier survival curves (upper) and GVHD score (lower) of mice after allo-BMT are presented. Data presented are from at least 3 independent experiments. (A,F) Data are presented as mean ± standard deviation; (C-D,G) data are presented as mean ± standard error of the mean. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, n.s.: not significant; unpaired t test with Welch’s correction (A,F), Spearman’s correlation (B), Kaplan-Meier survival analysis for survival, and analysis of variance for analysis of weight loss and GVHD score.

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