Limits...
Cell biology and clinical promise of G-CSF: immunomodulation and neuroprotection.

Xiao BG, Lu CZ, Link H - J. Cell. Mol. Med. (2007 Nov-Dec)

Bottom Line: G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis.Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration.Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. bgxiao@shmu.edu.cn

ABSTRACT
In the light of the enthusiasm to use of recombinant human granulocyte colony-stimulating factor (G-CSF) for immunomodulation and neuroprotection, it should be remembered that the current knowledge is based on a century of laborious research. G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis. Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration. Here, we describe the immunomodulation and the neuroprotection that can be achieved with G-CSF, and summarize possible mechanisms of G-CSF as a potential therapeutic agent in autoimmune diseases and neurological disorders. Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

Show MeSH

Related in: MedlinePlus

Possible mechanisms for G-CSF-mediated neuroprotection via immunomodulation. G-CSF polarizes T cell differentiation from Th1 to Th2 cells and induces Th2 responses, or relies on tolerogenic DC to generate regulatory T cells, which can enter into the CNS to contribute to the neuroprotective microenvironment through producing BDNF, IL-4, IL-10 and TGF-b. In addition, G-CSF, as an anti-inflammatory agent, can reduce levels of IFN-γ, IL-1β, IL-6, TNF-α and iNOS production in order to co-construct the neuroprotective microenvironment.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4401293&req=5

fig04: Possible mechanisms for G-CSF-mediated neuroprotection via immunomodulation. G-CSF polarizes T cell differentiation from Th1 to Th2 cells and induces Th2 responses, or relies on tolerogenic DC to generate regulatory T cells, which can enter into the CNS to contribute to the neuroprotective microenvironment through producing BDNF, IL-4, IL-10 and TGF-b. In addition, G-CSF, as an anti-inflammatory agent, can reduce levels of IFN-γ, IL-1β, IL-6, TNF-α and iNOS production in order to co-construct the neuroprotective microenvironment.

Mentions: The inflammation within the CNS is a common phenomenon even in classic non-inflammatory brain diseases that are characterized by trauma or degeneration of neuronal structures, such as stroke, Alzheimer disease, or Parkinson disease. The strategy for indirectly protecting neurons and axons partly through immunomodulation may improve the outcome of the patients. Protective autoimmunity is a relatively new concept. It refers to a benign autoimmune response that contributes to the maintenance and protection of injured neurons and the promotion of recovery after traumatic injury to the CNS [103]. Because G-CSF can polarize T cell differentiation from Th1 to Th2 cells and induce Th2 response (or regulatory T cells), an imagination has been proposed that systemic Th2 shift may promote neuroprotection and regeneration [103, 104] (Fig. 4). There are several lines of evidence that a Th2 switch is beneficial for the injured CNS: (1) Th2 cells support neuronal survival better than Th1 cells in vitro; (2) Th2 cells suppress Th1-induced inflammatory signals in brain slices in vitro and (3) Th2-inducing adjuvants such as aluminium hydroxide promote axon regeneration better than the Th1- inducing complete Freund's adjuvant (CFA). Potent inducers of a systemic Th2 switch such as statins support neuroprotection and/or regeneration. A recent review describes that the development of a Th1 response to myelin basic protein (MBP) is associated with worse neurological outcome after stroke while the induction of MBP-specific regulatory T cells is neuroprotective in the setting of stroke [105]. Based on such experiments, it could be that G-CSF plays a neuroprotective role through a Th2 switch or regulatory T cell production. However, extensive studies are still needed to investigate how a therapeutic Th2 switch promotes neuronal survival and axonal regeneration after CNS damage and what potential mechanisms may be involved.


Cell biology and clinical promise of G-CSF: immunomodulation and neuroprotection.

Xiao BG, Lu CZ, Link H - J. Cell. Mol. Med. (2007 Nov-Dec)

Possible mechanisms for G-CSF-mediated neuroprotection via immunomodulation. G-CSF polarizes T cell differentiation from Th1 to Th2 cells and induces Th2 responses, or relies on tolerogenic DC to generate regulatory T cells, which can enter into the CNS to contribute to the neuroprotective microenvironment through producing BDNF, IL-4, IL-10 and TGF-b. In addition, G-CSF, as an anti-inflammatory agent, can reduce levels of IFN-γ, IL-1β, IL-6, TNF-α and iNOS production in order to co-construct the neuroprotective microenvironment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401293&req=5

fig04: Possible mechanisms for G-CSF-mediated neuroprotection via immunomodulation. G-CSF polarizes T cell differentiation from Th1 to Th2 cells and induces Th2 responses, or relies on tolerogenic DC to generate regulatory T cells, which can enter into the CNS to contribute to the neuroprotective microenvironment through producing BDNF, IL-4, IL-10 and TGF-b. In addition, G-CSF, as an anti-inflammatory agent, can reduce levels of IFN-γ, IL-1β, IL-6, TNF-α and iNOS production in order to co-construct the neuroprotective microenvironment.
Mentions: The inflammation within the CNS is a common phenomenon even in classic non-inflammatory brain diseases that are characterized by trauma or degeneration of neuronal structures, such as stroke, Alzheimer disease, or Parkinson disease. The strategy for indirectly protecting neurons and axons partly through immunomodulation may improve the outcome of the patients. Protective autoimmunity is a relatively new concept. It refers to a benign autoimmune response that contributes to the maintenance and protection of injured neurons and the promotion of recovery after traumatic injury to the CNS [103]. Because G-CSF can polarize T cell differentiation from Th1 to Th2 cells and induce Th2 response (or regulatory T cells), an imagination has been proposed that systemic Th2 shift may promote neuroprotection and regeneration [103, 104] (Fig. 4). There are several lines of evidence that a Th2 switch is beneficial for the injured CNS: (1) Th2 cells support neuronal survival better than Th1 cells in vitro; (2) Th2 cells suppress Th1-induced inflammatory signals in brain slices in vitro and (3) Th2-inducing adjuvants such as aluminium hydroxide promote axon regeneration better than the Th1- inducing complete Freund's adjuvant (CFA). Potent inducers of a systemic Th2 switch such as statins support neuroprotection and/or regeneration. A recent review describes that the development of a Th1 response to myelin basic protein (MBP) is associated with worse neurological outcome after stroke while the induction of MBP-specific regulatory T cells is neuroprotective in the setting of stroke [105]. Based on such experiments, it could be that G-CSF plays a neuroprotective role through a Th2 switch or regulatory T cell production. However, extensive studies are still needed to investigate how a therapeutic Th2 switch promotes neuronal survival and axonal regeneration after CNS damage and what potential mechanisms may be involved.

Bottom Line: G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis.Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration.Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. bgxiao@shmu.edu.cn

ABSTRACT
In the light of the enthusiasm to use of recombinant human granulocyte colony-stimulating factor (G-CSF) for immunomodulation and neuroprotection, it should be remembered that the current knowledge is based on a century of laborious research. G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis. Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration. Here, we describe the immunomodulation and the neuroprotection that can be achieved with G-CSF, and summarize possible mechanisms of G-CSF as a potential therapeutic agent in autoimmune diseases and neurological disorders. Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

Show MeSH
Related in: MedlinePlus