Dietary glutamine modifies the effect of L‐asparaginase on lymphocyte populations in mice.

Abstract

L-asparaginase (ASNase) is used in the treatment of acute lymphoblastic leukemia. ASNase depletes plasma asparagine and glutamine, resulting in general immunosuppression. The objectives of this study were: to identify which cell populations in the spleen, thymus and bone marrow are targeted by ASNase, and to assess if supplementing the diet with glutamine modifies the effect of ASNase on normal lymphocyte populations. Mice freely consuming water +/− alanyl-glutamine dipeptide (AG, 0.05 M) were injected once daily with 0 or 3 IU/g BW E. Coli ASNase for 7d. Tissues were collected on d7 and prepared for analysis of cell surface markers by flow cytometry using a FACScan. ASNase inhibited BW gain and reduced cell numbers in spleen (−57%) and thymus (−54%). In bone marrow, ASNase reduced B220+ cells by 28%. In spleen, ASNase reduced CD19+ B cells to 21% of controls, decreased CD4+ and CD8+ T cells nearly in half, and diminished CD11b expression by 45%. In thymus, ASNase depleted double positive (CD4+CD8+) and single positive (CD4+CD8−, CD4−CD8+) T cells to 52% of controls; in contrast, numbers of immature (CD4−CD8−) T cells remained stable. Free consumption of 0.05 M AG partially reversed ASNase effects in spleen, but not thymus or bone marrow. In conclusion, ASNase reduces maturing populations of normal B and T cells. Dietary AG can modify some but not all of these effects. Funded by AICR.