J Immunol 2002 Feb 15;168(4):2011-2019
Zavala F, Abad S, Ezine S, Taupin V, Masson A, Bach JF.
Institut National de la Sante et de la Recherche Medical, Unite 25 and Unite 345, Necker Hospital, Paris, France. Sanofi-Synthelabo, Bagneux, France.
Converging evidence that G-CSF, the hemopoietic growth factor of the myeloid lineage, also exerts anti-inflammatory and pro-Th2 effects, prompted us to evaluate its direct therapeutic potential in autoimmune diseases.
Here we report a novel activity of G-CSF in experimental allergic encephalomyelitis, a murine model for multiple sclerosis, driven by Th1-oriented autoaggressive cells.
A short 7-day treatment with G-CSF, initiated at the onset of clinical signs, provided durable protection from experimental autoimmune encephalomyelitis.
G-CSF-treated mice displayed limited demyelination, reduced recruitment of T cells to the CNS, and very discrete autoimmune inflammation, as well as barely detectable CNS mRNA levels of cytokines and chemokines.
In the periphery, G-CSF treatment triggered an imbalance in the production by macrophages as well as autoreactive splenocytes of macrophage inflammatory protein-1[alpha] and monocyte chemoattractant protein-1, the prototypical pro-Th1 and pro-Th2 CC chemokines, respectively.
This chemokine imbalance was associated with an immune deviation of the autoreactive response, with reduced IFN-[gamma] and increased IL-4 and TGF-[beta]1 levels.
Moreover, G-CSF limited the production of TNF-[alpha], a cytokine also associated with early CNS infiltration and neurological deficit.
These findings support the potential application of G-CSF in the treatment of human autoimmune diseases such as multiple sclerosis, taking advantage of the wide clinical favorable experience with this molecule.