Eotaxin-2 blockade ameliorates experimental autoimmune encephalomyelitis

AIM: To study the effect of blocking the eo-2 pathwayon the development and severity of experimental autoimmune encephalomyelitis(EAE). METHODS: We produced m Ab directed against eo-2,named D8. MOG35-55 induced-EAE mice were dailyintravenously injected with either 25 μg or 100 μg D8,or with vehicle control alone [phosphate-buffered saline(PBS)], starting from day 0 post immunization and weremonitored for EAE clinical score(n = 10 in each group).Mice were sacrificed on day 58 and their sera were assessed for the presence of anti-myelin oligodendrocyteglycoprotein(anti-MOG) antibodies autoantibodies, aswell as for the profile of pro-inflammatory cytokines andchemokines. Histological analysis of brain sections wasperformed by hematoxylin and eosin staining.RESULTS: Daily treatment of EAE induced mice with D8 significantly decreased the severity of EAE symptoms. Treatment with both concentrations of D8 ameliorated EAE symptoms compared to PBS treated mice, starting from day 42 post immunization(0.89 ± 0.35 in D8 25 μg and D8 100 μg treated groups vs 2.11 ± 0.38 in the PBS treated group, P = 0.03). A significant improvement in EAE clinical score compared to total Ig G treated mice was observed with the higher concentration of D8(0.81 ± 0.38 in D8 100 μg treated group vs 2.11 ± 0.31 in Ig G1 treated group, on day 56 post immunization, P = 0.04). D8 treated mice with EAE did not significantly exhibit lower sera levels of anti-MOG autoantibodies compared to Ig G-treated mice. However, they expressed lower sera levels of the pro-inflammatory cytokines: tumor necrosis factor(7.8 ± 0.2 pg/m L in D8 100 μg treated mice vs 19.9 ± 3.4 pg/m L in Ig G treated mice, P = 0.005) and interferon-gamma(1.4 ± 0.6 pg/m L in D8 100 μg treated mice vs 3.6 ± 0.4 pg/m L in Ig G treated mice, P = 0.02), as well as reduced levels of the chemokine macrophage chemoattractant protein-1(27.2 ± 3.1 pg/m L in D8 100 μg treated mice vs 63.7 ± 12.3 pg/m L in Ig G treated mice, P = 0.03). These findings indicate that blocking the eo-2 pathway in EAE may affect not only eosinophil infiltration into the central nervous system(CNS), but also have an effect on monocytes and T cells, but not humoral, mediated responses. Histological analysis of the brains of D8 treated mice with EAE support that this treatment decreases immune cells infiltrates in the CNS.CONCLUSION: Taken together, these findings suggest a role for eo-2 in EAE pathogenesis and consequentially may support a therapeutic potential of anti-eo-2 neutralizing m Ab in multiple sclerosis.