Lactoferrin as an agent in the prevention of organ transplant rejection and graft-versus-host-disease
The present invention relates to methods of using lactoferrin (LF) to treat, prevent or reduce the incidence of organ transplant rejection and graft-versus-host-disease. More particularly, the present invention relates to methods of reducing an immune response against miss-matched transplanted organs such as kidney, heart, lung, liver, pancreas and stem cells by administering a composition of lactoferrin to the recipient patients. In addition, this invention relates to the treatment of bone marrow transplant (BMT) donors with lactoferrin to attenuate the development of graft-versus-host-disease in the recipients. Moreover, this invention relates to the treatment of xenograft organ donors with lactoferrin to attenuate the development of graft rejection in the recipients.
1. A method of treating tissue or organ transplant rejection in a recipient comprising the step of orally administering to the recipient an effective amount of a lactoferrin composition to attenuate the tissue or organ transplant rejection.
2. The method of claim 1 wherein said lactoferrin composition reduces allogeneic immune responses in the recipient.
3. The method of claim 1 , wherein the tissue is bone marrow or peripheral stem cells.
4. The method of claim 1 , wherein the organ is kidney, heart, lung, liver, or pancreas.
5. The method of claim 1 wherein said lactoferrin composition regulates T cell responses by inducing transplant tolerance in the recipient.
6. The method of claim 1 , wherein said lactoferrin composition is dispersed in a pharmaceutically acceptable carrier.
7. The method of claim 1 , wherein said lactoferrin is mammalian lactoferrin.
8. The method of claim 7 , wherein said lactoferrin is human or bovine.
9. The method of claim 1 , wherein said lactoferrin is recombinant lactoferrin.
10. The method of claim 1 , wherein said lactoferrin composition is administered parenterally.
11. The method of claim 1 further comprising administering an antacid in conjunction with said lactoferrin composition.
12. The method of claim 1 further comprising administering the lactoferrin in a delayed release formulation.
13. The method of claim 12 , wherein the lactoferrin release occurs in the small intestine.
14. The method of claim 12 , wherein the lactoferrin release occurs in the large intestine.
15. The method of claim 1 , wherein the amount of the lactoferrin composition that is administered is about 1 mg to about 20 g per day.
16. The method of claim 1 , wherein the amount of the lactoferrin composition that is administered is about 0.1 g to about 5 g per day.
17. The method of claim 1 , wherein said lactoferrin modulates the mucosal or systemic immune system in a subject by increasing the amount of lactoferrin in the gastrointestinal tract.
18. The method of claim 17 , wherein said lactoferrin stimulates interleukin-18 or MIP-3-alpha in the gastrointestinal tract.
19. The method of claim 17 , wherein said lactoferrin regulates the activity of immune cells.
20. The method of claim 17 , wherein the immune cells are B and T lymphocytes, antigen-presenting cells, natural killer cells, macrophages and granulocytes.
21. The method of claim 20 , wherein the T lymphocytes are selected from the group consisting of CD4+/CD3+, CD8+/CD3+ cells and NK-T cells.
22. The method of claim 17 , wherein said lactoferrin regulates the production or activity of pro-inflammatory cytokines.
23. The method of claim 1 further comprising administering a metal chelator dispersed in a pharmaceutically acceptable carrier.
24. The method of claim 23 , wherein the metal chelator is ethylenediaminoetetracacetic acid (EDTA) or [etheylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA).
25. The method of claim 24 , wherein the metal chelator is EDTA.
26. The method of sentence 25 , wherein the amount of EDTA that is administered is about 1 ng to about 1 g per day.
27. The method of claim 1 , further comprising administering an immunosuppressive agent, anti-rejection agent or anti-GVHD therapy in combination with the lactoferrin composition.
28. The method of claim 27 , wherein the immunosuppressive agent is selected from the group consisting of cyclosporine, prednisone, azathioprine, tacrolimus and mycophenolate mofetil.
29. A method of modulating the immune response against an organ or tissue transplant in a recipient comprising the step of orally administering to the recipient an effective amount of a lactoferrin composition to modulate the response against the organ or tissue transplant.
30. A method of treating graft-versus-host-disease in a recipient comprising the step of orally administering to the recipient an effective amount of a lactoferrin composition to attenuate the graft-versus-host-disease in the recipient.
31. The method of claim 30 further comprising treating ex vivo the donor organ or tissue with the lactoferrin composition.
32. The method of claim 30 , wherein the tissue is a stem cell.
33. The method of claim 30 , wherein the tissue is bone marrow or peripheral stem cells.
34. A method of treating graft-versus-host-disease comprising the step of orally administering an effective amount of a lactoferrin composition to the donor organ or donor tissue prior to transplantation into the recipient.
35. The method of claim 34 , wherein the tissue is a stem cell.
36. A method of treating tissue or organ transplant rejection in a recipient comprising the step of orally administering to the donor an effective amount of a lactoferrin composition to attenuate the tissue or organ transplant rejection in the recipient.