Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and other immunomodulatory therapies for the treatment of infectious diseases in solid organ transplant recipients.
OBJECTIVE
Infections continue to cause significant morbidity and mortality in SOT recipients despite major advances in immunosuppressive and antimicrobial regimens. Immunomodulatory cytokines provide a potential means to augment the host immune response to infection. This review will focus on cytokine therapy for the prophylaxis and treatment of infections in solid organ transplant recipients, and will speculate on the potential for further advances in the field.


RESULTS
In kidney and liver transplant recipients, granulocyte colony-stimulating factor (G-CSF) has been used successfully to reverse ganciclovir-induced neutropenia or cytomegalovirus-induced neutropenia. Although G-CSF also reversed corticosteroid-induced suppression of the neutrophil respiratory burst in vitro, prophylactic G-CSF failed to reduce infections or mortality in nonneutropenic solid organ transplant recipients. Published clinical experience with granulocyte-macrophage colony-stimulating factor (GM-CSF) in this population has been limited to case reports and a small case series, whereas the use of macrophage colony-stimulating factor (M-CSF) or interferon-gamma (IFN-gamma) has not been systematically investigated in controlled clinical trials.


CONCLUSIONS
Despite encouraging results in vitro and in preclinical models, immunomodulatory cytokines have not met expectations when administered to SOT recipients. Nonetheless, the principle of selective enhancement of innate immunity for the prevention and treatment of infections in this patient population has promise and warrants further study.
Page
Andrea V
AV
Division of Infectious Diseases, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Liles
W Conrad
WC
D000818:Animals; D003141:Communicable Diseases / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007371:Interferon-gamma / Q000627:therapeutic use; D009503:Neutropenia / Q000188:drug therapy / Q000276:immunology; D016377:Organ Transplantation / Q000009:adverse effects*; D011994:Recombinant Proteins; D016896:Treatment Outcome
D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor