title: Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy.
abstract: Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them "tolerogenic," which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility.
authors: 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois , Chicago, Illinois.
authors: Palash
authors: P
authors: Bhattacharya
authors: 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois , Chicago, Illinois.
authors: Isadore
authors: I
authors: Budnick
authors: 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois , Chicago, Illinois.
authors: Medha
authors: M
authors: Singh
authors: 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois , Chicago, Illinois.
authors: Muthusamy
authors: M
authors: Thiruppathi
authors: 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois , Chicago, Illinois.
authors: Khaled
authors: K
authors: Alharshawi
authors: 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois , Chicago, Illinois.
authors: Hatem
authors: H
authors: Elshabrawy
authors: 2 Department of Surgery, College of Medicine, University of Illinois , Chicago, Illinois.
authors: Mark J
authors: MJ
authors: Holterman
authors: 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois , Chicago, Illinois.
authors: Bellur S
authors: BS
authors: Prabhakar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy; D015551:Autoimmunity; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D016178:Granulocyte-Macrophage Colony-Stimulating Factor