P320 - SYNERGISTIC EFFECT OF GLUTAMINE/SITAGLIPTIN COMBINATION AGAINST ACUTE GRAFT-HOST DISEASE IN MICE

P320

SYNERGISTIC EFFECT OF GLUTAMINE/SITAGLIPTIN COMBINATION AGAINST ACUTE GRAFT-HOST DISEASE IN MICE

F. Vandamme^1,2,*, S. Plet², N. Benzekri¹, D. SEGUY^1,2

¹CHU de Lille, ²INFINITE U1286 Inserm, Lille, France

Rationale: We have previously shown that oral glutamine (Gln 1% in drinking water) has a protective effect against intestinal acute graft-host disease (GvHD) in mice. A recent study reported a low incidence of GvHD in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) receiving sitagliptin (Sita), an inhibitor of dipeptidyl peptidase-4. We evaluated the protective role of Sita, alone or combined with oral Gln, against GvHD damage in mice.

Methods: Between d-7 and d7 (sacrifice), female B6D2F1 mice received oral Gln 2% and/or Sita 40 mg/kg/d by gavage () or drinking water only (H2O). After total body irradiation on d-1 (2×450 cGy), 2×10⁶ T cells and 5x10⁶ HSC either allogeneic (A) or syngeneic (S), necessarily or never inducing GVHD, respectively, were infused on d0. On d7, a clinical score (CS) was recorded, ileal histology was performed (villus height (VH), crypt depth (CD), crypt apoptosis (CA, n_Crypt+/n_Crypt) using TUNEL method), and aerobic bacterial translocation (BT) was measured in liver cultures (median [Q1-Q3], Mann-Whitney test).

Results: Compared to control mice (A-H2O), treated groups (A-Gln, A-Sita, A-Sita/Gln) showed reduced intestinal damage, with higher VH (µm) (167[117-179] vs. 188[146-206], 186[132-205], 198[143-209], p<0.001), less deeper CD (µm) (122[65-145] vs. 111[66-125], 109 [64-123], 105[60-121], p<0.008) and lower CA (%) (50[47-57] vs. 32[31-33], 33[25-37], 20[15-28], p<0.006). Compared to the S-H2O group, the parameters deteriorated after A transplant, except in the following situations where they were comparable: CS and BT in A-Gln; VH, CA and BT in A-Sita/Gln

Conclusion: Individually, Gln and Sita reduce intestinal damage associated with GvHD after A transplant, and their combination shows a synergistic effect such that VH, CA and BT were comparable to S-H2O group which could not experience any GvHD.

Disclosure of Interest: None declared