Potential of colony-stimulating factors to improve host defense in organ transplant recipients

Abstract

Purpose of review Although immunosuppressive drugs prevent graft rejection, they also predispose patients to infection, representing a major complication in organ transplantation. It would thus be highly desirable to attain true immune tolerance without increasing the risk of infections and malignancies. Before the background of current strategies in the management of infections, the novel concept of differential reactivation of immunity, ie, boosting the innate immune response while continuing suppression of the adaptive immune response, is introduced. Recent findings Present clinical experience, feasibility, and potential risks of applying factors that potentially display such dichotomal properties (eg, granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF]) are discussed. Summary In dexamethasone-treated PBMC isolated from control patients, or in cells obtained from immunosuppressed liver transplant patients, GM-CSF was found to selectively restore the innate immune response, without activating the specific immune response implicated in graft rejection. Moreover, GM-CSF efficiently restored the immune response against an otherwise lethal bacterial infection in immunosuppressed mice, without inducing the rejection of a skin transplant. These recent data could have implications for clinical practice and suggest a more detailed evaluation of agents with similar actions to GM-CSF in the restoration of innate immunity in organ transplant patients.