Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Immunol. Mar 27, 2013; 3(1): 7-14
Published online Mar 27, 2013. doi: 10.5411/wji.v3.i1.7
Eotaxin-2 blockade ameliorates experimental autoimmune encephalomyelitis
Karin Mausner-Fainberg, Arnon Karni, Jacob George, Michal Entin-Meer, Arnon Afek
Karin Mausner-Fainberg, Arnon Karni, Department of Neurology, The Neuroimmunology Laboratory, 64239 Tel Aviv, Israel
Jacob George, Department of Cardiology, Kaplan Medical Center, Rehovot, 64239 Tel Aviv, Israel
Michal Entin-Meer, Department of Cardiology, TASMC, 64239 Tel Aviv, Israel
Karin Mausner-Fainberg, Arnon Karni, Jacob George, Michal Entin-Meer, Arnon Afek, Sackler’s Medical School, Tel Aviv University, 64239 Tel Aviv, Israel
Arnon Afek, Sheba Medical Center, Tel Hashomer, 52621 Ramat Gan, Israel
Author contributions: All the authors contributed equally to this paper.
Correspondence to: Dr. Arnon Karni, Department of Neurology, The Neuroimmunology Laboratory, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 64239 Tel Aviv, Israel. arnonk@tasmc.health.gov.il
Telephone: +97-2-3-6973424 Fax: +97-2-3-6974380
Received: November 3, 2011
Revised: March 12, 2012
Accepted: December 23, 2012
Published online: March 27, 2013

AIM: To study the effect of blocking the eo-2 pathway on the development and severity of experimental autoimmune encephalomyelitis (EAE).

METHODS: We produced mAb directed against eo-2, named D8. MOG35-55 induced-EAE mice were daily intravenously 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 were monitored 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 oligodendrocyte glycoprotein (anti-MOG) antibodies autoantibodies, as well as for the profile of pro-inflammatory cytokines and chemokines. Histological analysis of brain sections was performed 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 IgG 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 IgG1 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 IgG-treated mice. However, they expressed lower sera levels of the pro-inflammatory cytokines: tumor necrosis factor (7.8 ± 0.2 pg/mL in D8 100 μg treated mice vs 19.9 ± 3.4 pg/mL in IgG treated mice, P = 0.005) and interferon-gamma (1.4 ± 0.6 pg/mL in D8 100 μg treated mice vs 3.6 ± 0.4 pg/mL in IgG treated mice, P = 0.02), as well as reduced levels of the chemokine macrophage chemoattractant protein-1 (27.2 ± 3.1 pg/mL in D8 100 μg treated mice vs 63.7 ± 12.3 pg/mL in IgG 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 mAb in multiple sclerosis.

Keywords: Multiple sclerosis, Experimental autoimmune encephalomyelitis, Eotaxin-2, Neutralizing monoclonal antibodies