Oral Human Recombinant Lactoferrin Prevents Acute Graft-Versus-Host Disease And Stimulates Reconstitution Of Donor Bone Marrow-Derived T-Cells In A Mouse Model Of Bone Marrow Transplantation
Year: 2010
Type: article
Abstract: Lactoferrin, an iron-binding protein with multiple physiological functions (anti-microbial, anti-inflammatory, and immunomodulatory), is a component of mammalian milk. Lactoferrin has immune modulatory effects through interaction with natural killer cells, T-cells and interfering with cytokine production. There is in vitro evidence that lactoferrin can reduce lipopolysaccaride-induced release or pro-inflammatory cytokines in mice and human possibly through scavenging lipopolysaccaride (LPS) in the intestinal lumen. The central hypothesis of this research project was that administration of human recombinant lactoferrin (hrLF) to mice undergoing allogeneic bone marrow transplantation (allo BMT) will reduce the pro-inflammatory effects of the conditioning regimens, and gut epithelial tissue damage, resulting in less non-specific activation of donor T-cells that cause GvHD. Irradiated (11 Gy) C57BL/6 recipient received 5×106 T cell depleted (TCD) bone marrow cells and 3×106 plastic non-adherent splenocytes from naïve BA.B10 congenic donors. To test the hypothesis we studied the effect of oral hrLF administration on GvHD in murine models of allo BMT. Lactoferrin (hrLF) (75 mg/mouse) or PBS was administered by gastric gavage from day -4 for up to 30 days in surviving recipients. GvHD was monitored clinically by using criteria such as weight reduction and diarrhea. Survival was assessed. Flow cytometry was used to determine donor chimerism, immune reconstitution and the frequency of naive CD62L+ T cells. Oral hrLF reduced acute GvHD and the experimental group survived 100%; however, 67% of the control group survived. There was a significant difference in the number of peripheral blood nucleated cells (PBNC) and bone marrow nucleated cells (BMNC) between the experimental and control groups (p=0.02 and p=0.01). No significant difference in bone marrow CD4+ and CD8+ T-cells, and CD4+CD62L+ T-cells from donor spleen derived cells between two groups was found. Oral hrLF treatment successfully controlled GvHD and suppressed donor T-cells. There were significant differences between lactoferrin group and the control mice including diarrhea, weight loss, and numbers of nucleated cells. Hence, prophylactic use of lactoferrin is a novel therapeutic approach for prophylaxis of GvHD in patients undergoing allogeneic HSCT.
Authors: M. Akhtari, S.M. Hossain, P. Forghani, E.K. Waller
Institutions: Emory University, Winship Cancer Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W1993594992