The role of
glia maturation factor (
GMF) in
myelin oligodendrocyte glycoprotein (MOG) 35-55
peptide-induced
experimental autoimmune encephalomyelitis (EAE) was investigated using
GMF-deficient (
GMF-KO) mice. We demonstrate that
GMF-KO mice were resistant to the MOG 35-55
peptide-induced EAE as compared to wild type (Wt) mice (two in eight versus 10 in 10). Next, we examined the effect of administration of recombinant human
GMF (rGMF) on MOG 35-55
peptide-induced EAE in mice. Daily administration of rGMF, staring days 1-14, resulted in significant exacerbation of clinical symptoms. Following rGMF
injections, both
GMF-KO (six in eight) and Wt mice (eight in eight) developed severe EAE (maximal clinical score of 3.5-4.0) with high frequency. The histological examination revealed severe infiltration of inflammatory cells in the spinal cord of MOG-immunized Wt mice while the resistance to EAE in
GMF-KO mice was characterized by the absence of inflammatory cells. Administration of rGMF in Wt mice and
GMF-KO mice resulted in a significant increase in infiltrating cells in the spinal cord following MOG-immunizations. We also evaluated
cytokines and
chemokines production as parameters of severity of
inflammation in the spinal cord of Wt versus
GMF-KO mice with and without
GMF-reconstitution following MOG-immunizations.
Cytokines (TNF-α, IFN-γ, IL-1β, IL-6) and
chemokines (CCL2, CCL3, CXCL10,
GM-CSF) production were significantly greater in Wt mice than in
GMF-KO mice following MOG-immunization. Furthermore, the reconstitution experiment with rGMF showed that the administration of rGMF in both, Wt mice and
GMF-KO mice produced significant increase in the
GMF-mediated
cytokine/
chemokine production.