Additive effects of combination treatment with anti-inflammatory and neuroprotective agents in experimental autoimmune encephalomyelitis

We studied the effects of combination treatment with an anti-inflammatory agent, interferon (IFN)-β, and a putative neuroprotective agent, an estrogen receptor (ER)-β ligand, during EAE. Combination treatment significantly attenuated EAE disease severity, preserved axonal densities in spinal cord, and reduced CNS inflammation. Combining ERβ treatment with IFNβ reduced IL-17, while it abrogated IFNβ-mediated increases in Th1 and Th2 cytokines from splenocytes. Additionally, combination treatment reduced VLA-4 expression on CD4+ T cells, while it abrogated IFNβ-mediated decreases in MMP-9. Our data demonstrate that combination treatments can result in complex effects that could not have been predicted based on monotherapy data alone.