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Overview of immunosuppressive agents used for prevention and treatment of graft-versus-host disease

Nelson J Chao, MD
Section Editor
Robert S Negrin, MD
Deputy Editor
Alan G Rosmarin, MD


Graft-versus-host disease (GVHD) is the result of an intricate immune response following allogeneic stimuli. GVHD, which can be acute and/or chronic, occurs when T cells of the donor recognize the presence of histocompatibility antigens in the host that differ from those of the donor cells. This initial antigen recognition is followed by amplification of the T cell recognition process.

The proliferation of activated T cells leads to the production and secretion of a variety of cytokines, which are responsible for the inflammatory effects and tissue damage associated with GVHD [1]. Much of the damage is caused by inflammatory cytokines, such as interleukin (IL)-1, IL-2, tumor necrosis factor (TNF), and gamma-interferon [2]. Use of immunosuppressive agents such as cyclosporine, tacrolimus (FK506), and sirolimus have delineated the critical events that lead to the activation of these alloreactive T cells and the subsequent amplification of the signals involved in T cell proliferation. These laboratory studies have led to an understanding of the mechanisms of action of specific immunosuppressants. Further, such understanding allows for the development and testing of novel immunosuppressive agents.

This topic review will focus on the most commonly used commercially available immunosuppressive drugs for prevention and/or treatment of GVHD. Discussions of the pathogenesis, clinical manifestations, diagnosis, prevention, and treatment of acute and chronic GVHD are found elsewhere in the program. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and "Clinical manifestations, diagnosis, and grading of chronic graft-versus-host disease" and "Treatment of chronic graft-versus-host disease" and "Prevention of acute graft-versus-host disease".)


Corticosteroids — Corticosteroids are the most widely used "front-line" therapy for the treatment of clinical GVHD. Drugs of this class have been combined with other immunosuppressants in the prophylaxis against GVHD. However, we still do not fully understand their mechanism of action. This has resulted in empiricism in the development of therapeutic doses and anecdotal reports of efficacy in certain clinical settings.

Mechanism of action — The most commonly utilized corticosteroid is methylprednisolone, which differs from prednisolone and prednisone only by the addition of a 6-alpha-methyl group. The 6-alpha-methyl group blocks the specific binding of this corticosteroid to transcortin, the protein that transports steroids in the plasma. Instead, methylprednisolone is primarily bound to albumin. The frequent side effects from methylprednisolone may be dependent on the albumin level in the host.

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Literature review current through: Dec 2017. | This topic last updated: Sep 14, 2017.
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