Immunomodulatory approaches to augment phagocyte-mediated host defense for treatment of infectious diseases

Neutrophils, monocytes, and tissue-based macrophages are major cellular components of the innate immune system, which represents the initial line of host defense against invading pathogens. Four cytokines-granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interferon-gamma (IFN-gamma)--have received increasing attention as potential adjunctive immunomodulatory agents for treatment of infectious diseases. Studies conducted in vitro and in vivo have shown that G-CSF, GM-CSF, and IFN-gamma can augment the functional antimicrobial activities of neutrophils. Similarly, GM-CSF, M-CSF, and IFN-gamma up-regulate multiple antimicrobial mechanisms in monocytes and macrophages. Studies conducted in animal models have shown the potential use of each of these cytokines for the treatment of infections caused by a variety of bacterial, fungal, and parasitic diseases. Because clinical experience with these immunomodulatory cytokines is relatively limited and currently investigational, controlled clinical trials will be necessary to define specific indications for the administration of these cytokines in therapeutic regimens.